ArticleLiterature Review

COVID-19 Vaccine: A comprehensive status report

August 2020
Virus Research 288(14, April):198114

DOI:10.1016/j.virusres.2020.198114

Authors:

Simran Preet Kaur

All India Institute of Medical Sciences

Vandana Gupta

Ram Lal Anand College University of Delhi

The current COVID-19 pandemic has urged the scientific community internationally to find answers in terms of therapeutics and vaccines to control SARS-CoV-2. Published investigation mostly on SARS-CoV and to extent on MERS has taught lessons to vaccination strategies to this novel coronavirus. This is attributed to the fact that SARS-CoV-2 uses the same receptor as SARS-CoV on host cell i.e. human Angiotensin Converting Enzyme 2 (hACE2) and is approximately 79% similar genetically to SARS-CoV. Though the efforts on COVID-19 vaccines started very early, initially in China, as soon as the outbreak of novel coronavirus erupted and then world-over as the disease was declared a pandemic by WHO. But we will not be having an effective COVID-19 vaccine before September, 2020 as per very optimistic estimates. This is because a successful COVID-19 vaccine will require a cautious validation of efficacy and adverse reactivity as the target vaccinee population include high-risk individuals over the age of 60, particularly those with chronic co-morbid conditions, frontline healthcare workers and those involved in essentials industries. Various platforms for vaccine development are available namely: virus vectored vaccines, protein subunit vaccines, genetic vaccines, and monoclonal antibodies for passive immunization which are under evaluations for SARS-CoV-2, with each having discrete benefits and hindrances. The COVID-19 pandemic which probably is the most devastating one in the last 100 years after Spanish flu mandates the speedy evaluation of the multiple approaches for competence to elicit protective immunity and safety to curtail unwanted immune-potentiation which plays an important role in the pathogenesis of this virus. This review is aimed at providing an overview of the efforts dedicated to an effective vaccine for this novel coronavirus which has crippled the world in terms of economy, human health and life.

Global research landscape on nanotechnology in acute lung injury: a bibliometric analysis

Article

Full-text available

Mar 2025

Background Acute lung injury is a common respiratory emergency that seriously affects the life, health and quality of life of patients, especially after the global COVID-19 pneumonia. The application of nanotechnology in acute lung injury is promising. In response to the knowledge explosion resulting from rapid publication growth, we applied bibliometric analysis to explore the research profile and thematic trends in the field. Methods Articles and reviews related to nanotechnology in acute lung injury from 2004 to 2023 were searched. Java-based Citespace, VOSviewer, and R software-based Bibiometrix were used to systematically evaluate publications by spatiotemporal distribution, author distribution, subject categories, topic distribution, references, and keywords. Results A total of 1,347 publications were included. The number of papers related to nanotechnology in acute lung injury has grown exponentially over the past 20 years. China was the most productive country out of all 53 countries, followed by the United States. The Chinese Academy of Sciences was the most productive institution with 76 papers. PARTICLE AND FIBRE TOXICOLOGY was the most productive journal. The top five high-frequency keywords were inflammation, oxidative stress, toxicity, in vitro , respiratory-distress-syndrome. And the top five emerging keywords were delivery, covid-19, extracellular vesicles, therapy, sars-cov-2. Drug delivery are the focus of current research. Two emerging research areas represented the development trends: novel nanocarriers with higher efficiency and lower biotoxicity, and the other is research related to impact of nanomaterials in the progression of acute lung injury. Conclusion The field of nanotechnology in acute lung injury has been in a period of rapid development in the last three years. Delivery,targeted delivery and exosm have been the focus of current research in this field. Two emerging research areas represented the development trends:novel nanocarriers with higher efficiency and lower biotoxicity such as extracellular vesicles, exosomes and solid lipid nanoparticles, and the other is research related to impact of nanomaterials in the progression of acute lung injury.

Factors influencing COVID-19 vaccine acceptability among household heads in northern Nigeria: a community-based cross-sectional study

Article

Full-text available

Jan 2025

Objectives COVID-19 vaccine was rolled out for the public in August 2021 in Zamfara state, Northen Nigeria. We determined the factors influencing COVID-19 vaccine acceptance. Settings We executed a community-based analytical cross-sectional study during the first 4 months of the second phase of the COVID-19 (Oxford/AstraZeneca) mass vaccination campaign in Zamfara state. Participants We used multistage sampling to select 910 household heads. Outcome measures We used a semistructured electronic questionnaire to collect data on sociodemographic characteristics, uptake and acceptance of COVID-19 vaccine between 12 October and 20 December 2021. We calculated frequencies, proportions, adjusted ORs and 95% CIs for factors influencing COVID-19 vaccine acceptance using logistic regression. Results Our respondents had a median age of 48 years (IQR: 37–55), 78.1% (711) were men, a majority more than 30 years, and only 8.9% (81) had received COVID-19 vaccine. Of the 829 unvaccinated respondents, 10.1% (84) accepted to take the vaccine, the current week of the interview while 12.2% (101) rejected the vaccine. Individuals aged 30 years and older (adjusted OR (aOR)=2.39, 95% CI 1.16 to 4.94, p=0.018), who owned a mobile phone (aOR=25.35, 95% CI 11.23 to 57.23, p<0.001) and a television (aOR=3.72, 95% CI 1.09 to 12.69, p=0.036), with medium–high levels of trust (aOR=7.41, 95% CI 3.10 to 17.74, p<0.001), and those with a medium–high (positive) levels of attitude (aOR=1.82, 95% CI 1.06 to 3.11, p=0.029) were more likely to accept the COVID-19 vaccine. Also, those who had been vaccinated with other vaccines (aOR=2.2, 95% CI 1.09 to 4.43, p=0.027) and those previously tested for COVID-19 (aOR=2.0, 95% CI 1.10 to 3.66, p=0.023) were also more likely to accept it. Conclusion COVID-19 vaccine had a poor uptake and acceptance. Factors such as age, awareness, trust and previous vaccination experience played a significant role in COVID-19 vaccine acceptance. We recommended targeted public health campaigns, improving community engagement and building trust in community leaders, healthcare providers and public health institutions.

COVID-19 Mobile Applications for Vaccination in New York State (NYS)

Conference Paper

Jan 2025

Exploring the expensive therapeutic potential and clinical applications of viruses severe acute respiratory syndrome (SARS)-COV-2

Article

Full-text available

Dec 2024

In this review research, the full bio-medical potential and application of the severe acute respiratory syndrome (SARS)-CoV-2 viruses are discussed in detail with the aim of discovering innovative treatment strategies in virology and medicine. The SARS-CoV-2 which caused an international health crisis also unraveled an opportunity to gain from its pathogenic effects to treat the affected people. The study aims at testing whether the newly discovered SARS-CoV-2 can be used for therapeutic and clinical purposes. With in-depth analytics, this investigation issue endeavors to unearth new ways of fighting infectious diseases and to improve existing medical interventions. Beside scientific and practical significance the role of this work is vital. By learning the biologic and molecular mysteries of SARS-CoV-2, the researchers can create precise medicines and vaccines not only against COVID-19 but also the other infectious diseases as well. Furthermore, this recommendation may open the door to the future development of gene therapy and vaccine technology. In this sense, it combines multiple approaches, such as viral studies, immunology, and molecular biology. Laboratory experiments, computer program modeling and clinical trials are applied to detection of the SARS-COV-2 in therapeutic implementation. The principal conclusion and analysis of this research put forth the fact that SARS-CoV-2 can be utilized in anti-viral treatment, cancer therapy, and vaccine programs. The study results confirm the inherent adaptability of viruses like SARS-CoV-2 and emphasis on the development of specific therapeutic measures. It is valuable because of its potential to add to virology and medication, showing new ways for virus-based treatment. In addition, the impact of these results on treatments would be revolutionary, with potential to invent superior and flexible interventions against infectious disease. In short, the therapeutic use of SARS-CoV-2 can be regarded as a bold innovation with tremendous consequences for general health, and ultimately for medical science.

COVID-19 vaccines: current and future challenges

Article

Full-text available

Nov 2024

As of December 2020, around 200 vaccine candidates for Coronavirus Disease 2019 (COVID-19) are being developed. COVID-19 vaccines have been created on a number of platforms and are still being developed. Nucleic acid (DNA, RNA) vaccines, viral vector vaccines, inactivated vaccines, protein subunit vaccines, and live attenuated vaccines are among the COVID-19 vaccine modalities. At this time, at least 52 candidate vaccines are being studied. Spike protein is the primary protein that COVID-19 vaccines are targeting. Therefore, it is critical to determine whether immunizations provide complete or fractional protection, whether this varies with age, whether vaccinated people are protected from reoccurring diseases, and whether they need booster shots if they’ve already been inoculated. Despite the enormous achievement of bringing several vaccine candidates to market in less than a year, acquiring herd immunity at the national level and much more so at the global level remains a major challenge. Therefore, we gathered information on the mechanism of action of presently available COVID-19 vaccines in this review and essential data on the vaccines’ advantages and downsides and their future possibilities.

PROFIL SUBKLAS IGG PADA INDIVIDU PENERIMA VAKSIN COVID19 PLATFORM VEKTOR VIRUS

Article

Full-text available

Jan 2025

Respon imun pasca vaksinasi COVID19 beragam dikarenakan proses pembuatan vaksin yang dipercepat untuk mengatasi pandemi COVID19 yang ada. Tujuan penelitian adalah untuk mendapatkan data respon imun seluler individu pasca vaksinasi COVID19 vektor virus sebagai data penunjang kebijakan vaksinasi COVID19 di Indonesia. Metode penelitian yang akan dilaksanakan adalah penggunaan bahan baku tersimpan (BBT) berupa plasma dari individu yang menerima vaksin COVID19 vektor virus yang diambil pada enak titik waktu yang berbeda. Metode Elisa digunakan untuk menilai kadar subklas immunoglobulin G yang ada dalam plasma individu yang menerima vaksinasi COVID19. Uji repeated one-way ANOVA atau Uji Firedman digunakan untuk menganalisa rerata beda kadar subklas IgG pada 4 kelompok berdasarkan waktu. Hasil menunjukkan bahwa subklas IgG1 mendominasi kadar keseluruhan subklas IgG pada keenam titik point waktu. Terdapat perbedaan yang bermakna kadar IgG1 dan IgG2 berdasarkan waktu (p<0,0001), namun tidak ditemukan perbedaan yang bermakna pada subklas IgG3 (p=0,276) dan IgG4 (p=0,967). Penelitian ini menunjukkan bahwa kadar subklas IgG1 dan IgG2 dapat dijadikan penanda peningkatan imunitas individu penerima vaksin COVID19 vektor virus.

Lipid-based vaccines against viruses including COVID-19

Chapter

Jan 2025

LESSONS LEARNED: AN IN-DEPTH LOOK AT SINO PHARM VACCINE RESEARCH IN KARACHI PAKISTAN OBSERVATIONAL STUDY

Article

Full-text available

Feb 2025

Background: The global COVID-19 pandemic has led to widespread efforts in developing effective vaccines to control the spread of SARS-CoV-2. The Sinopharm BBIBP-CorV vaccine, an inactivated virus vaccine developed by the Beijing Institute of Biological Products, received emergency use authorization from the World Health Organization (WHO). Despite its global distribution, limited real-world safety data exist for specific populations, particularly in low- and middle-income countries like Pakistan. Objective: This study aimed to evaluate the safety profile and incidence of adverse events following immunization (AEFI) associated with the Sinopharm vaccine among the population of Karachi, Pakistan. Methods: A prospective observational study was conducted over 56 days, including 5,420 participants vaccinated with the Sinopharm BBIBP-CorV vaccine. Data were collected using structured questionnaires and follow-up interviews, focusing on demographic information, comorbidities, and post-vaccination adverse effects. Descriptive statistics were applied to assess the frequency and severity of AEFI, while chi-square tests evaluated associations between adverse events and demographic factors. Results: Out of 5,420 vaccinated individuals, 24 (0.442%) reported adverse effects. Of these, 23 cases (95.8%) occurred after the first dose and 1 case (4.2%) after the second dose. Female participants accounted for 79.2% of AEFI cases, while males represented 20.8%. The most affected age group was 41–50 years, comprising 45.8% of AEFI cases. Common adverse effects included headache (41.7%), vertigo (20.8%), and dizziness (16.7%). Comorbidities such as hypertension and diabetes showed no significant association with AEFI occurrence. Conclusion: The Sinopharm vaccine demonstrated a strong safety profile, with mild and self-limiting adverse effects observed in a small fraction of participants. These findings support its continued use in mass immunization campaigns, reinforcing its role as a reliable tool against COVID-19.

UNDERSTANDING THE RISK PERCEPTION OF COVID-19 VACCINE AMONG ADULTS WITH COMORBIDITIES

Article

Full-text available

Feb 2025

With the vaccination rollout in the Philippines to lessen the transmission and mitigate the effects of the virus during the emergence of the COVID-19 pandemic in late 2019 up until 2022, Filipinos had different perceptions of vaccination. The study focused on understanding the risk perception of the COVID-19 vaccine among adults with comorbidities in Cagayan de Oro City. Despite limited previous studies that tackled the COVID-19 virus that was rampant during the commencement of this study, similar studies showed differences in how people perceived vaccination rollout during a major health crisis, e.g., Polio or influenza. The study used the Health Belief Model’s constructs (perceived susceptibility, perceived severity, perceived barriers, perceived benefits, cues to action, and self-efficacy) in crafting a research instrument, a virtual in-depth interview, that aimed to identify the risk perception of the COVID-19 vaccine among respondents that had comorbidities in Cagayan de Oro. These respondents were identified through a snowball sampling method and the researchers used the data collected from the interviews to assess their risk perception of the vaccine. The themes that emerged from the transcriptions of the interviews were used for data analysis. The results indicate that the respondents had high perceived susceptibility, benefits, and severity. Unvaccinated respondents showed high self-efficacy for getting vaccinated. The various perceived barriers identified in this study against COVID-19 vaccination mainly include health issues, the effectiveness of the vaccine, and external influence. Finally, the respondents’ cues to action are affected by their perceived severity, susceptibility, barriers, and benefits.

New-onset discoid lupus erythematosus after Oxford- AstraZeneca adenoviral (Covishield ™ ) vaccination in a paediatric patient

Article

Full-text available

Feb 2025

Oxford Astra-Zeneca adenoviral vaccine (Covishield ™) is a viral vector vaccine that uses an attenuated, non-replicating strain of Chimpanzee adenovirus as a vector to carry the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human cells. Although highly effective against SARS-CoV-2 infection coronavirus disease 19 (COVID-19), COVID-19 vaccines have been implicated in triggering and exacerbating various autoimmune diseases due to their role in inciting antigen-specific immune responses. There have been various reports of the development or exacerbation of dermatomyositis and systemic lupus erythematosus (LE) following COVID-19 vaccine. Here, we present the rare case of the development of discoid LE (DLE) in a 14-year-old female patient 3 weeks following the administration of the first dose of Covishield ™ (ChAdOx1 nCoV-19 vaccine). The patient also had positive anti-nuclear antibody titres. The temporal relationship of her symptoms after vaccine administration could suggest a possible association between the vaccine and the development of DLE, as this is the time interval for antibody formation post-vaccine.

Assessment of COVID-19 Vaccination Uptake Among Healthcare Workers in Garowe, Puntland State, Somalia

Article

Full-text available

Nov 2023

The emergence of SARS-CoV-2 led to a global crisis, prompting the development of COVID-19 vaccines. While initial vaccine candidates received WHO approval, vaccine acceptance varied globally. In Somalia, healthcare workers' acceptance remained unexplored. This study aimed to assess vaccination uptake among healthcare workers in Garowe, Puntland State, Somalia. This study employed a cross-sectional design to assess COVID-19 vaccination uptake among healthcare workers in Garowe, Puntland State, Somalia. Conducted over six months in Garowe City, the study included physicians, nurses, midwives, pharmacists, and lab technicians from public andprivate hospitals. Employing a multi-stage randomized sampling technique, data was collected via structured questionnaires and analyzed using SPSS version 22.0. The analysis included descriptive statistics, chi-square tests, and logistic regression. Factors like age [χ2=0.398], sex [χ2=2.162], marital status[χ2=0.487], and living status [χ2=0.170] displayed no significant association [p>0.05] with vaccination status. However, education [χ2=7.435*], knowledge about vaccine efficacy against different variants of covid-19 [χ2=12.704*], vaccine administration to individuals with health conditions[χ2=6.472*], understanding of vaccine mechanisms [χ2=7.584*], perceived effectiveness[χ2=64.872*], and concern about adverse effects[χ2=9.145*] are significantlyassociated [p<0.05] with vaccination status. Notably, despite initial significance, adjusted models showed varying associations. This research highlighted nuanced factors influencing vaccination uptake among healthcare workers. Demographics did not directly affect vaccination status, emphasizing the importance of awareness, confidence, and specific vaccine knowledge. Tailorededucational programs and targeted interventions could enhance vaccine acceptance among healthcare professionals, necessitating ongoing monitoring and adaptation of strategies.

RNA diagnostics and therapeutics: a comprehensive review

Article

Full-text available

Jan 2025

RNA-focused therapy and diagnostics have been making waves in molecular biology due to the advantages RNA has over DNA; for instance, the ability of RNA to target nearly any genetic component in the cell is a big step in treating disorders. Moreover, RNA-based diagnosis of diseases is only becoming increasingly popular, especially after the COVID-19 pandemic, which brought up the need for cost-effective and efficient diagnosing kits for the vast majority. RNA-based techniques also have close to no risk of genotoxicity and can efficiently target undruggable regions of the cell. RNA treatments have effectively shown the future of the medical industry in the past couple of decades, and they will only be seen to improve. This review paper provides an overview on the different techniques that use RNA-based approaches in the field of diagnostics and therapeutics.

Recombinant Anti-PF4 Antibodies Derived from Patients with Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) Facilitate Research and Laboratory Diagnosis of VITT

Article

Full-text available

Dec 2024

Background/Objectives: Adenoviral vector-based vaccines against COVID-19 rarely cause vaccine-induced immune thrombocytopenia and thrombosis (VITT), a severe adverse reaction caused by IgG antibodies against platelet factor 4 (PF4). To study VITT, patient samples are crucial but have become a scarce resource. Recombinant antibodies (rAbs) derived from VITT patient characteristic amino acid sequences of anti-PF4 IgG are an alternative to study VITT pathophysiology. Methods: Amino acid sequences of the variable region of immunoglobulin light and heavy chain of anti-PF4 IgG derived from VITT patients were obtained by mass spectrometry sequencing and rAbs were synthetized by reverse-engineering. Six different rAbs were produced: CR23003, CR23004, and CR23005 (from a patient vaccinated with Jcovden, Johnson & Johnson-Janssen (Beerse, Belgium)), CR22046, and CR22050 and CR22066 (from two different patients vaccinated with Vaxzevria, AstraZeneca (Cambridge, UK)). These rAbs were further characterized using anti-PF4 and anti-PF4/heparin IgG ELISAs, rapid anti-PF4 and anti-PF4/polyanion chemiluminescence assays, and PF4-induced platelet activation assay (PIPA) and their capacity to induce procoagulant platelets. Results: rAbs bound to PF4 alone, but not to PF4/polyanion complexes in rapid chemiluminescence assays. Chemiluminescence assays and both anti-PF4 IgG and anti-PF4 IgG/heparin ELISA showed concentration-dependent PF4 binding of all six rAbs, however, with different reactivities among them. PIPA showed a similar, concentration-dependent platelet activation pattern. rAbs varied in their reactivity and the majority of the tested rAbs were able to induce procoagulant platelets. Conclusions: The six rAbs derived from VITT patients reflect VITT-typical binding capacities and the ability to activate platelets. Therefore, these rAbs offer an attractive new option to study VITT pathophysiology.

Experiencias y desafíos de la Comisión nacional asesora de eventos supuestamente atribuibles a la vacunación o inmunización graves de Ecuador, 2020-2023

Article

Dec 2024

RESUMEN Objetivo Describir las experiencias de la Comisión Nacional Asesora de Eventos Supuestamente Atribuibles a la Vacunación o Inmunización (ESAVI) graves implementada en Ecuador en el período 2020-2023. Método Se realizó un informe que analiza la implementación, el funcionamiento y los resultados de la Comisión Nacional Asesora sobre ESAVI graves en Ecuador. Se realizó un análisis cuantitativo de los registros de vacunación y un análisis cualitativo con base en testimonios de expertos, que recoge las experiencias directas y desafíos operacionales enfrentados por los miembros de la Comisión. Resultados La implementación de la Comisión ha permitido el registro y el análisis sistemático de los ESAVI graves. De 256 casos notificados, se analizaron 139; 59% como eventos coincidentes; 16,6% no clasificables; 6,5% indeterminados; 5% como eventos por estrés; 3,6% como eventos relacionados con un error programático, y 9,4% relacionados con la vacuna, que incluyeron alergias, síndrome de Guillain-Barré y trombosis, entre otros. Los testimonios de los expertos destacaron la necesidad de mejorar la capacitación del personal y la infraestructura tecnológica, y compartieron que la Comisión desempeñó un papel crucial en la vigilancia de la seguridad de las vacunas, además de incrementar la confianza de la población en los procesos de vacunación. Conclusiones La Comisión Nacional Asesora ha sido esencial en la vigilancia de la seguridad de las vacunas en Ecuador, ya que garantiza la notificación, el análisis de causalidad y la investigación de los ESAVI graves. Se identificaron desafíos que deberán ser abordados para mantener la confianza pública en los programas de vacunación.

An evolutionary game theory approach to modeling behavioral interaction in disclosing infection begins with an outbreak: COVID-19 as an example

Preprint

Full-text available

Oct 2024

The global impact of the COVID-19 pandemic on the livelihoods of people worldwide prompted the implementation of a range of preventive measures at local, national, and international levels. Early in the outbreak, before the vaccine became accessible, voluntary quarantine and social isolation emerged as crucial strategies to curb the spread of infection. In this research, we present a game-theoretic model to elucidate the voluntary disclosure of exposure to infected individuals within communities. By employing a fractional derivative approach to illustrate disease propagation within the compartmental model, we determine the minimum level of voluntary disclosure required to disrupt the chain of transmission and allow the epidemic to fade. Our findings suggest that higher transmission rates and increased perceived severity of infection change the externality of disclosing infected exposure, thereby contributing to a rise in the proportion of individuals opting for quarantine and reducing disease incidence. We estimate behavioral parameters and transmission rates by fitting the model to hospitalized cases in Chile, South America. Results from our paper underscore the potential for public health authorities to influence and regulate voluntary disclosure of infection during emerging outbreaks through effective risk communication, emphasizing the severity of the disease, and providing accurate information about hospital capacity to the public.

Comparative Analysis of SARS-CoV-2 Antibodies in Diabetic and Non-Diabetic Healthcare Workers Post-Infection and Vaccination

Article

Full-text available

Jun 2024

Prediction of COVID-19 Vaccine Side Effects using SMOTE and Ensemble Machine Learning Models

Article

Apr 2024

While the rapid development of vaccines during the COVID-19 pandemic helped save billions of lives, a significant percentage of the population reported adverse reactions after vaccination. Post-vaccination surveys were conducted to understand the possible side effects. Analyzing and understanding the side effects enables the relevant stakeholders to gain more understanding of the vaccine and allows the individual to make informed decisions about whether to receive the vaccine. This work aims to identify a robust approach that can be used to predict the possibility of potential adverse symptoms. A dataset comprising 840 participants with 15 Post-Vaccination Symptoms was considered for the study. Synthetic Minority Oversampling TEchnique (SMOTE) was used to handle the class imbalance of the dataset. A combination of SMOTE and ensemble machine learning models was used to predict the adverse reactions to COVID-19 vaccines. The ensemble Machine Learning (ML) models that are considered for this study are Random Forest, Extreme Gradient Boosting Machine (XGBoost), Light Gradient Boosting Machine, and AdaBoost. The metrics accuracy, precision, recall and Receiver Operating Characteristic-Area Under the Curve (ROC-AUC) were used to measure the performance of the models. The dataset was pre-processed to handle missing values and one-hot encoding was applied to convert categorical variables into the numerical format. Insights into the data distribution and relationships between variables were gained through exploratory data and correlation analysis, respectively. Class imbalance in the target variables was addressed using SMOTE, resulting in a significantly improved F1-score and ROC-AUC score. Among the ensemble ML models, XGBoost delivered the best performance metrics. A combined performance score was calculated by averaging the F1-score and accuracy to identify the best model. XGBoost obtained the highest performance score among the ensemble ML models, and its performance is further enhanced by performing the threshold adjustment using the maximum F1- score strategy. The findings suggest that the combination of SMOTE and ensemble learning models with threshold adjustment provides a more efficient prediction of adverse effects after COVID-19 vaccination, aiding in healthcare decision-making.

Determining the ultraviolet radiation dose experienced by aerosols using ultraviolet-sensitive dyes

Article

Full-text available

May 2024

The application of ultraviolet (UV)-light-based air disinfection methods holds promise but also presents several challenges. Among these, the quantitative determination of the required UV radiation dose for aerosols is particularly significant. This study explores the possibility of determining the UV dose experienced by aerosols without the use of virus-containing aerosols, circumventing associated laboratory safety issues. To achieve this, we developed a model system comprised of UV-sensitive dyes dissolved in di-ethyl-hexyl-sebacate (DEHS), which facilitates the generation of non-evaporating and UV-degradable aerosols. For the selection of UV-sensitive dyes, 20 dyes were tested, and 2 of them were selected as being the most suitable, according to several selection criteria. Dye-laden aerosol droplets were generated using a commercial aerosol generator and subsequently exposed to UV-C radiation in a laboratory-built UV irradiation chamber. We designed a low-pressure impactor to collect the aerosols pre- and post-UV exposure. Dye degradation, as a result of UV light exposure, was then analyzed by assessing the concentration changes in the collected dye solutions using a UV-visible spectrophotometer. Our findings revealed that a UV dose of 245 mW s cm-2 resulted in a 10 % degradation, while a lower dose of 21.6 mW s cm-2 produced a 5 % degradation. In conclusion, our study demonstrates the feasibility of using aerosol droplets containing UV-sensitive dyes to determine the UV radiation dose experienced by an aerosol.

Broad-spectrum coronavirus neutralization induced by hetero RBD-Fc protein vaccine

Article

Sep 2024
J MED VIROL

In the landscape of infectious diseases, human coronaviruses such as SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2 pose significant threats, characterized by severe respiratory illnesses and notable resistance to conventional treatments due to their rapid evolution and the emergence of diverse variants, particularly within SARS‐CoV‐2. This study investigated the development of broad‐spectrum coronavirus vaccines using heterodimeric RBD‐Fc proteins engineered through the “Knob‐into‐Hole“ technique. We constructed various recombinant proteins incorporating the receptor‐binding domains (RBDs) of different coronaviruses. Heterodimers combining RBDs from SARS‐CoV‐2 with those of SARS‐CoV or MERS‐CoV elicited superior neutralizing responses compared to homodimeric proteins in murine models. Additionally, heterotetrameric proteins, specifically D614G_Delta/BA.1_XBB.1.5‐RBD and MERS_D614G/BA.1_XBB.1.5‐RBD, elicited remarkable breadth and potency in neutralizing all known SARS‐CoV‐2 variants, SARS‐CoV, related sarbecoviruses like GD‐Pangolin and WIV1, and even MERS‐CoV pseudoviruses. Furthermore, these heterotetrameric proteins also demonstrated enhanced cellular immune responses. These findings underscore the potential of recombinant hetero proteins as a universal vaccine strategy against current and future coronavirus threats.

Vaccine Targeted Prophylaxis For Covid-19: A Comprehensive Review

Article

Full-text available

Sep 2024

The Impact of COVID-19 Vaccination Side-Effects on Work Attendance among Saudi Healthcare Workers

Article

Full-text available

Aug 2024
Infect Dis Rep

Objective: This cross-sectional-survey-based study aimed to investigate the severity of side-effects from Coronavirus disease (COVID-19) mRNA (Pfizer, Moderna), viral vector DNA (Oxford-AstraZeneca, J&J/Janssen), inactivated virus (Sinopharm, Sinovac), and other vaccines among healthcare workers (HCWs) in Saudi Arabia, focusing on their impact on work attendance. Methods: A total of 894 HCWs residing in Saudi Arabia participated in this study from March 2023 to May 2023. Participants completed an online questionnaire assessing demographic information, vaccination status, comorbidities, vaccine side-effects, and missed work information after vaccination. Descriptive statistics and chi-square tests were used for data analysis. Results: The majority of participants were female (83.7%) and aged 25–34 years (42.8%). Most participants were predominantly vaccinated with mRNA vaccines. Common side-effects included pain at the injection site, fatigue, fever, and chills. However, no significant association was found between vaccine type, side-effects, and work absenteeism. While demographic factors such as age and healthcare profession did not influence work absenteeism, variations were observed among different racial groups. Conclusion: COVID-19 vaccination among HCWs in Saudi Arabia is associated with common side-effects, but their impact on work attendance is not significant. Understanding these implications can inform strategies to support the healthcare workforce and mitigate the impact on patient care and staffing during the ongoing COVID-19 pandemic.

MANIFESTASI KULIT SETELAH VAKSIN COVID-19: SEBUAH TINJAUAN SISTEMATIS DAN METAANALISIS

Article

Full-text available

Aug 2024

Pendahuluan: Penyakit coronavirus 2019 (COVID-19) yang telah terjadi hingga saat ini mendorong pemerintah dan berbagai negara untuk melakukan vaksinasi sebagai cara untuk melawan virus COVID-19. Hingga akhir Mei 2021, lebih dari 1,5 miliar dosis vaksin telah diberikan di seluruh dunia diikuti dengan bukti nyata adanya efek samping pada kulit terkait dengan penggunaan vaksin COVID-19. Tujuan: Mengetahui bukti terbaru dan pengetahuan dari manifestasi kulit yang terkait dengan kejadian setelah vaksinasi COVID-19 selama vaksinasi massal dapat membantu tenaga kesehatan dalam edukasi pasien. Metode: Pencarian dilakukan secara komprehensif pada topik yang menilai manifestasi kulit setelah vaksinasi covid-19 dari awal hingga mei 2022. Hasil: Terdapat 15 penelitian dari total 917 pasien yang menunjukan reaksi kulit yang paling sering terjadi setelah vaksin covid-19 adalah COVID-ARM (58,2%), urtika (22,3%), morbilliform eruption (10,6%), pitiriasis like rosea (6,1%), dan VZV Reactivation (2,6%). Dari hasil systematic review dan metaanalisis juga menunjukkan reaksi kulit yang dialami paling banyak terjadi pada wanita, middle-aged, setelah vaksin pertama (vaccine based mRNA) dengan onset 1-21 hari setelah vaksinasi. Kesimpulan: Manifestasi kulit yang didapat setelah vaksin covid-19 terutama vaksin berbasis mRNA hampir sebagian besar hanya terbatas pada area tempat suntikan (COVID-ARM), dapat sembuh dengan sendirinya tanpa pengobatan, dan tidak ada gejala sistemik yang berbahaya.

Feasibility Study of Applying Spatial Crowd Smoothing Without Economic Incentives on Ticket Reservation System that Applies Nudges

Article

Aug 2024

In this study, we devise several seat selection screens for a movie theater ticket reservation system that applies nudges to achieve spatial crowd smoothing without relying on economic incentives. We design three types of nudges that achieve the following: (i) render seats in less-crowded areas noticeable; (ii) present social norms; and (iii) suggest seats in less-crowded areas to people who have selected seats in crowded areas. Results of verification experiment show that (ii) the presentation of social norms is generally effective in avoiding congestion regardless of the ticket sales and (ii) the text of the presented social norms is more effective in avoiding congestion when it contains motivational sentences than when it is verbally expressed. Furthermore, the results indicate that (i) rendering seats in less-crowded areas more conspicuous and (iii) suggesting seats in less-crowded areas to those who select seats in more crowded areas may be effective in avoiding congestion, depending on the ticket sales. Consequently, the feasibility of spatial crowd smoothing without relying on economic incentives for the seat selection screen of a ticket reservation system that applies nudges is demonstrated.

When should lockdown be implemented? Devising cost-effective strategies for managing epidemics amid vaccine uncertainty

Article

Full-text available

Jul 2024
PLOS COMPUT BIOL

During an infectious disease outbreak, public health policy makers are tasked with strategically implementing interventions whilst balancing competing objectives. To provide a quantitative framework that can be used to guide these decisions, it is helpful to devise a clear and specific objective function that can be evaluated to determine the optimal outbreak response. In this study, we have developed a mathematical modelling framework representing outbreaks of a novel emerging pathogen for which non-pharmaceutical interventions (NPIs) are imposed or removed based on thresholds for hospital occupancy. These thresholds are set at different levels to define four unique strategies for disease control. We illustrate that the optimal intervention strategy is contingent on the choice of objective function. Specifically, the optimal strategy depends on the extent to which policy makers prioritise reducing health costs due to infection over the costs associated with maintaining interventions. Motivated by the scenario early in the COVID-19 pandemic, we incorporate the development of a vaccine into our modelling framework and demonstrate that a policy maker’s belief about when a vaccine will become available in future, and its eventual coverage (and/or effectiveness), affects the optimal strategy to adopt early in the outbreak. Furthermore, we show how uncertainty in these quantities can be accounted for when deciding which interventions to introduce. This research highlights the benefits of policy makers being explicit about the precise objectives of introducing interventions.

Undesirable effects of COVID-19 vaccination on Saudi population: A descriptive study, Winter 2022

Article

Full-text available

Jan 2024

Objective The development of coronavirus disease 2019 (COVID-19) vaccines was a crucial preventative measure toward controlling the pandemic. Several side effects have been reported. This study investigated the long-term side effects reported by the Saudi population. post-COVID-19 vaccination. Methods The cross-sectional study involved Saudi participants of both genders, aged ≥16 years, and had received at least one dose of any of the available vaccines in Saudi Arabia. They were asked to fill out an online questionnaire divided into three sections: Demographics, medical history, and side effects that appeared post-COVID-19 vaccines. Results The findings indicated that the undesirable effects were reported by 82% of the participants. These side effects involve three categories: The most common, additional or reported, and persistent side effects. The most common side effects were pain at the site of injection (88.16%), bone pain/joint pain (68.7%), and fatigue (68.46%). Menstrual disorders (n = 46), hair loss (n = 34), and memory problems (n = 19) were reported by participants as additional side effects. Among all side effects, fatigue, joint pain, hair loss, and menstrual disorders were the most persistent side effects. Moreover, 190 participants reported that they were diagnosed with diseases soon after receiving the COVID-19 vaccine including COVID-19, thyroid gland disorder, and irritable bowel disease. The quality of life of some of the participants was affected by post-COVID-19 vaccines, as 25.28% had anxiety, 21.22% had depression, and 33.16% had discomfort. Conclusion These findings may contribute to understanding the effect of COVID-19 vaccines on the Saudi population’s health and public opinion about these vaccines.

UHDJST Rebin 20220820 V3

Article

Full-text available

Jul 2024

Từ khóa: Tính an toàn; COVID-19

Article

Full-text available

Jun 2024

Mục tiêu: Đánh giá tính an toàn của vaccine Nanocovax (VCNC) 25mcg phòng COVID-19 do Nanogen sản xuất trên người Việt Nam tình nguyện ≥ 18 tuổi. Phương pháp nghiên cứu: Thử nghiệm lâm sàng ngẫu nhiên có đối chứng, mù đôi, giai đoạn 1, 2, 3 trên người tình nguyện khỏe mạnh từ ≥ 18 tuổi, tiêm theo phác đồ 2 liều cách nhau 28 ngày với VCNC hoặc giả dược. Đánh giá an toàn ở các thời điểm 60 phút, 7 ngày liên tục và 28 ngày sau tiêm. Kết quả: 13.266 người tình nguyện (9.043 người tiêm vaccine và 4.223 người tiêm giả dược) sau mũi tiêm 1 và 2, các biến cố xuất hiện với tần suất cao nhất ở nhóm vaccine và nhóm giả dược tại các thời điểm: Sau tiêm 60 phút thấy đau tại chỗ tiêm (lần lượt: 2,43-2,72% và 1,36-1,06%); tương tự, 7 ngày sau tiêm, biến cố tại chỗ là đau (lần lượt: 35,7-20,79% và 37,3-21,27%), đau cơ toàn thân (lần lượt: 20,50-10,80% và 22,77-11,19%). Tỷ lệ đối tượng có bất kỳ biến cố bất lợi nghiêm trọng trong nghiên cứu là 1,02% (136/13.226 đối tượng). Không có trường hợp nào tử vong liên quan tới sản phẩm nghiên cứu. Kết luận: VCNC với liều 25mcg đạt yêu cầu về an toàn trên người tình nguyện. Abstract Objectives: To evaluate the safety of the Nanocovax vaccine with a dose of 25mcg against COVID-19 produced by Nanogen in Vietnamese volunteers aged 1 Học viện Quân y 2 Viện Nghiên cứu Y Dược học Quân sự, Học viện Quân y * Tác giả liên hệ: Phạm Ngọc Hùng (pnhungqy@vmmu.edu.vn) Ngày nhận bài: 18/01/2024 Ngày được chấp nhận đăng: 26/3/2024 http://doi.org/10.56535/jmpm.v49i5.715

Mortality rates among vaccinated and unvaccinated covid19 patients in Duhok hospitals, Kurdistan Region, Iraq

Article

Full-text available

Jun 2024

Background and objectives: The corona virusvaccines are important in controlling the pandemic. In Kurdistan Region of Iraq three types of vaccines are available; Pfizer, AstraZeneca and SinoPharm. The objectiveof the study was to determine the effect of vaccine on severity and mortality rate among Covid-19 cases in Duhok, Iraq. Methods: In this Prospective study, 470 of hospitalized covid19 cases in Duhok, Iraqi Kurdistan between 1st june 2021 to 1st june 2022 were enrolled. Demographic parameters including age, sex, and past medical history of chronic diseases were taken. The severity of cases was assessed based on respiratory rate, oxygen saturation, and percentage of chest involvement by CT scan. The types and doses of vaccines received by patients were recorded. The patients were followed-up by the outcome (recovered and discharged from the hospital or dead). Results: The mean age of the patients was 64.98 years. The males were (51.49%, n=242) and females (48.51%, n=228). The majority of them did not receive any type of vaccines (81.49%, n=383). Most of the vaccinated patients received Pfizer vaccine. In term of Covid-19 severity, the study showed (65.75%, n=309) had mild-moderate disease and (34.26, n= 161) had severe disease. Moreover, the mortality rate was lower among vaccinated patients compared with unvaccinated patients 24.14% to 40.73% respectively. The study revealed that having the severe cases and being old were considered the main independent predictor of mortality among the patients (p value <0.0001). Conclusions: Vaccinated patients had lower chance of severe chest involvement, oxygen requirement and death rate compared to unvaccinated patients in our study.

Covid-19 vaccine uptake and its associated factors among adult population in Dangila district, Awi Zone, Northwest Ethiopia: A mixed method study

Article

Full-text available

May 2024
PLOS ONE

Introduction Vaccination is the most cost-effective approach that significantly reduces morbidity and mortality related to Coronavirus disease -19 (COVID-19). Nevertheless, there is a lack of information on the COVID-19 vaccine uptake and related factors in Ethiopia including the research area. Objective To assess COVID-19 vaccine uptake and its associated factors among adult population in Dangila District, Awi Zone, Northwest Ethiopia, 2023. Methods A community-based mixed-type study design was conducted from Oct, 15-Nov 15/2022. The study population was chosen using the multistage stratified random sampling technique for the quantitative study and the purposive sampling method for the qualitative inquiry. The collected data were managed and analyzed using SPSS version 25. Bivariable and multivariable logistic regressions were employed to identify factors associated with vaccine uptakes. In the qualitative part of the study, key informant interview was applied. After the interview was listened, the transcripts were coded and categorized into themes, and analyzed using Atlas.ti 7 software. Finally, the finding was triangulated with the quantitative results. Result The vaccine uptake among the adult population was found to be 47% (95% CL: 42.7%, 51.0%). History of having test for COVID-19 (AOR: 1.70, 95% CI: 1.02, 2.84), good knowledge about COVID-19 vaccine (AOR; 3.12, 95% CI; 2.11, 4.59), no formal education (AOR: 1.78, 95%: 1.26, 2.58), good attitude (AOR: 3.21, 95% CI: 2.13, 4.89), being in poor Income category (AOR: 1.83, 95% CI: 1.08, 3.06), being female (AOR: 1.75, 95% CI: 1.2, 2.58) and living in rural area (AOR: 3.1, 95% CI: 1.87, 5.12) were significantly associated with vaccine uptake rate. The study also identified that misperceptions about the vaccine efficacy and safety, availability of vaccine, lack of knowledge about the vaccine, mistrust of the corona virus vaccine, fear of adverse effects, social media influence and religious beliefs were found to be barriers of COVID -19 vaccine uptake. Conclusion In the Dangila district, adult population vaccination uptake for COVID-19 was comparatively low. To raise the rate of vaccination uptake, interventions must focus on the identified modifiable factors.

Enhancing Vaccine Quality and Accessibility: Strategies for Efficient Storage and Distribution in Resource-Constrained Environment

Article

Full-text available

Apr 2025

This study examines the challenges of vaccine quality and accessibility in resource-limited regions, where inadequate infrastructure and funding hinder effective storage and distribution. Vaccines play a crucial role in public health, but their efficacy is often compromised by logistical issues, particularly in low- and middle-income countries (LMICs). The review identifies key obstacles in maintaining a robust cold chain, which is essential for preserving vaccine integrity. It highlights innovative strategies to address these challenges, including optimizing cold chain systems, enhancing community outreach initiatives, and leveraging technological advancements such as solar-powered refrigerators and real-time monitoring tools. By synthesizing recent research and practical examples, this review underscores the importance of collaboration among stakeholders—governments, NGOs, and local communities—in improving vaccine distribution networks. Addressing these logistical challenges is essential for achieving vaccination targets and advancing global health equity. Ultimately, this study contributes to the discourse on enhancing immunization efforts in regions facing significant barriers, emphasizing the need for ongoing innovation and investment in vaccine delivery systems to ensure equitable access to life-saving vaccines.

COVID-19: Perspectives on innate immune evasion

Chapter

Mar 2024

Advances in Virus Biorecognition and Detection Techniques for the Surveillance and Prevention of Infectious Diseases

Article

Full-text available

Mar 2025

Viral infectious diseases pose a serious threat to global public health due to their high transmissibility, rapid mutation rates, and limited treatment options. Recent outbreaks of diseases such as plague, monkeypox, avian influenza, and coronavirus disease 2019 (COVID-19) have underscored the urgent need for efficient diagnostic and surveillance technologies. Focusing on viral infectious diseases that seriously threaten human health, this review summarizes and analyzes detection techniques from the perspective of combining viral surveillance and prevention advice, and discusses applications in improving diagnostic sensitivity and specificity. One of the major innovations of this review is the systematic integration of advanced biorecognition and detection technologies, such as bionanosensors, rapid detection test strips, and microfluidic platforms, along with the exploration of artificial intelligence in virus detection. These technologies address the limitations of traditional methods and enable the real-time monitoring and early warning of viral outbreaks. By analyzing the application of these technologies in the detection of pathogens, new insights are provided for the development of next-generation diagnostic tools to address emerging and re-emerging viral threats. In addition, we analyze the current progress of developed vaccines, combining virus surveillance with vaccine research to provide new ideas for future viral disease prevention and control and vaccine development, and call for global attention and the development of new disease prevention and detection technologies.

Mathematical analysis of COVID-19 dynamics in Iraq utilising empirical data

Article

Full-text available

Mar 2025

A Novel Mathematical Modelling of the COVID-19 Pandemic Including the Vaccination Campaign

Thesis

Sep 2022

The coronavirus (Covid-19) pendemic has extremely thrented to the health and lives of people all over the world. In this brief time frame, numerous illustrative investigations have been led to the numerical demonstration and examination of Covid-19. A few investigations have been taken into account for the vaccination process. This study aims at novel mathematical modeling of the Covid-19 pandemic including the vaccination campaign. A mathematical model about the Covid-19 is developed in the form of first-order ordinary differential equations(ODEs). In the numerical simulations, the parameter values will be taken from the literature, and estimations will be used to perform the solutions of the proposed model. Fourth-order Runge-Kutta numerical scheme will be applied to obtain the results. Additionally, Matlab will be utilized to examine the significance of mathematical outcomes for the model under consideration. Mathematical modeling with computational simulations is an important tool to estimates key transmission parameters and predicts model dynamics of the disease. Thus, during these specific circumstances, a numerical model is developed to show the impacts of the vaccination process, which has been performed recently on Covid-19 in this review. In the proposed model, just as the vaccinated individuals, a five-dimensional compartment system including the susceptible, infected, exposed and recovered population is built. Also, other than the positivity, existence and uniqueness of the solution, biologically feasible region will be discussed in detail. The basic reproduction number known as expected secondary infection, which is the expected infection among the susceptible populations caused by this infection, will also introduced. Results will be plotted graphically by Matlab to check the validity of the model and to compare with the results as available in the literature.

A review of SARS-CoV-2 virology, vaccines, variants and their impact on the COVID-19 pandemic

Article

Jan 2024

A novel coronavirus, named severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has spread in Wuhan, China, and caused the global pandemic infectious disease. This disease has been known as coronavirus disease 2019 (COVID-19). It continued to spread around the world and created outrageous effects on the healthcare and economic system throughout the world. Various strategies have been designed to diminish the morbidity and mortality of this infectious disease. Among them, the development of vaccines is the most effective method to prevent and treat the viral infection. Novel vaccines have been developed and proved to be effective in multiple clinical reports indicating a significant decline in the risk of COVID-19 infection. However, the emergence of new variants of SARS-CoV-2 with immune-evasive characteristics raised questions concerning the effectiveness of the vaccines. This review provides a brief introduction to developed vaccines, as well as emerging variant strains and vaccine effectiveness against these variants. In this article, we also reviewed the general biological features of SARS-CoV-2 and its pathogenesis and explained the clinical symptoms, transmission, diagnostic and treatment approaches to monitor and control emerging COVID-19 infection.

Linking COVID-19 and cancer: Underlying mechanism

Article

Nov 2024
BBA-MOL BASIS DIS

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lead to a global health crisis with a spectrum of clinical manifestations. A potentially vulnerable category for SARS-CoV-2 infection was identified in patients with other medical conditions. Intriguingly, parallels exist between COVID-19 and cancer at the pathophysiological level, suggesting a possible connection between them. This review discusses all possible associations between COVID-19 and cancer. Expression of receptors like angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) increases COVID-19 susceptibility. SARS-CoV-2 infection might increase cancer susceptibility and accelerate cancer progression through mechanisms involving cytokine storm, tissue hypoxia, impaired T-cell responses, autophagy, neutrophil activation, and oxidative stress. These mechanisms collectively contribute to immune suppression, hindered apoptosis, and altered cellular signaling in the tumor microenvironment, creating conditions favorable for tumor growth, metastasis, and recurrence. Approved vaccines and their impact on cancer patients along-with new clinical trials are also described.

Biotecnología aplicada al diagnóstico y tratamiento de la COVID

Article

Apr 2022

Introducción: el virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), que produce una patología llamada COVID-19 (Coronavirus Disease 2019), presenta cuadros diversos, desde los completamente asintomáticos hasta neumonías fatales. Debido, además, a su alta tasa de transmisión ha provocado una pandemia de consecuencias históricas. Objetivo: analizar los aportes derivados de la Biotecnología que resultaron en productos terapéuticos, diversas estrategias/técnicas disponibles actualmente para el diagnóstico y vacunas profilácticas destinadas a esta patología. Materiales y Métodos: se realizó una búsqueda en MEDLINE/Pubmed y otros buscadores, usando como palabras clave: COVID 19, SARS-CoV-2, coronavirus, vaccines, biopharmaceuticals, biotherapies, microbiota, y biomarkers. Resultados: en el trabajo se presentan y describen el desarrollo de tests diagnósticos, biofármacos, bioterapias con células madre distintas tecnologías y plataformas vacunales para COVID 19. Conclusiones: La biotecnología bioquímico-farmacéutica tiene una activa e importante participación en la Covid-19, a través de desarrollos que pueden prevenir, diagnosticar, tratar síntomas y disminuir la mortalidad de los pacientes.

Investigation of the thermal degradation of indinavir sulfate

Article

Oct 2024
J THERM ANAL CALORIM

The thermal behavior of the antiviral drug indinavir sulfate was investigated by TG/DTG, TG/DTA, DSC, hot stage microscopy and TG-FTIR. TG curve indicated the loss of water followed by four decomposition steps after melting at 150 °C. DSC curves on heat–cool–heat mode showed no evidence of recrystallization of the drug on cooling. From thermoanalytical techniques, mass spectrometry and characterization of the evolved gases, it was suggested that the decomposition starts with the release of water, carbon dioxide, isocyanic acid, ammonia, 2-indanol and 2-pentanol. At higher temperatures, the release of water, isocyanic acid, carbon dioxide, ammonia and 2-pentanol was observed. In addition, carbonyl sulfide was also present as a gaseous product of thermal decomposition and detected by the first time. Mass spectra of the sample heated up to 150 °C confirmed the release of 2-indanol and ammonia just after melting. Finally, a complete description of the thermal behavior of the drug is presented based on all these results.

Identification of Novel Allosteric Sites of SARS-CoV-2 Papain-Like Protease (PLpro) for the Development of COVID-19 Antivirals

Article

Sep 2024
J BIOL CHEM

Coronaviruses such as SARS-CoV-2 encode a conserved papain-like protease (PLpro) that is crucial for viral replication and immune evasion, making it a prime target for antiviral drug development. In this study, three surface pockets on SARS-CoV-2 PLpro that may function as sites for allosteric inhibition were computationally identified. To evaluate the effects of these pockets on proteolytic activity, 52 residues were separately mutated to alanine. In Pocket 1, located between the Ubl and thumb domains, the introduction of alanine at T10, D12, T54, Y72, or Y83 reduced PLpro activity to <12% of that of WT. In Pocket 2, situated at the interface of the thumb, fingers, and palm domains, Q237A, S239A, H275A, and S278A inactivated PLpro. Finally, introducing alanine at five residues in Pocket 3, between the fingers and palm domains, inactivated PLpro: S212, Y213, Y251, K254, and Y305. Pocket 1 has a higher druggability score than Pockets 2 and 3. MD simulations showed that interactions within and between domains play critical roles in PLpro activity and thermal stability. The essential residues in Pockets 1 and 2 participate in a combination of intra- and inter-domain interactions. By contrast, the essential residues in Pocket three predominantly participate in inter-domain interactions. The most promising targets for therapeutic development are Pockets one and 3, which have the highest druggability score and the largest number of essential residues, respectively. Non-competitive inhibitors targeting these pockets may be antiviral agents against COVID-19 and related coronaviruses.

Uncovering the coronavirus outbreak: present understanding and future research paths

Article

Sep 2024
J Basic Clin Physiol Pharmacol

Introduction The review discusses the pathophysiological mechanisms of SARS-CoV-2, the modes of transmission, and the long-term health consequences of COVID-19, emphasizing the importance of research and successful public health initiatives. Content COVID-19 taxonomy, pathophysiology, symptomatology, and epidemiological importance are the key objects of this research paper. This review explains how COVID-19 affects different systems of the body, including respiratory, cardiovascular, and reproductive systems of the human body. It describes the modes of entry of the virus into the cell; more precisely, ACE2 and TMPRSS2 in viral entry. In addition, the present study analyzes the situation of COVID-19 in India regarding vaccine development and the transmission rate related to socioeconomic factors. Summary The manifestation of COVID-19 presents a lot of symptoms and post-acute problems, issues which are seriously impacting mental health and physical health as well. The present review summarizes current research into pathogenicity and the mode of virus transmission, together with immunological responses. Coupled with strong vaccination programs, public health initiatives should hold the key to fighting this pandemic. Outlook Long-term effects and the development of treatment methods will need further study, as ambiguities on COVID-19 remain. Multidisciplinary collaboration across healthcare sectors in this respect is of paramount importance for the prevention of further spread and protection of public health.

Scalable bioprocess for the high-yield production of SARS-CoV-2 trimeric spike protein-based immunogen (IMT-CVAX) using suspension CHO cells

Article

Aug 2024
PROCESS BIOCHEM

The COVID-19 pandemic has brought global attention towards the readiness of biotechnology platforms for rapid development of immunogens to be used as vaccine antigens, in diagnostics and in fundamental research. In the present study we provide a bioprocess that is both robust and industry-compatible for high level expression, efficient purification, and scale-up of IMT-CVAX, a prefusion-stabilized trimeric spike protein of SARS-CoV-2. The recombinant IMT-CVAX protein was produced using stable cell pool of Chinese Hamster Ovary (CHO) cells that were banked in compliance with cGMP (Current Good Manufacturing Practices) regulations. High quantity expression of IMT-CVAX was achieved through optimization of the shake flask-based process with regards to media, nutrient feeding regimen, incubation temperature, viable cell density and cell viability. We employed refined expression procedures to scale up IMT-CVAX using bioreactor, resulting in a significantly higher yield of around 500 mg/L. Subsequently, a straightforward and simple purification process was developed to produce high-quality IMT-CVAX protein. This procedure consisted of centrifugation, tangential flow filtration (TFF), and either one- or two-step liquid chromatography. A robust anti-spike IgG response was observed in mice after immunization with purified adjuvanted IMT-CVAX. In pseudoviral neutralization assay, mice-generated anti-IMT-CVAX sera could neutralize various SARS-CoV-2 variants. The human convalescent sera from COVID-19-recovered patients recognized IMT-CVAX effectively, which confirms the conformational integrity of IMT-CVAX epitopes. The bioprocess demonstrated here is able to produce sufficient quantities of biopharmaceutical-quality spike protein, which can be used as immunogen against emerging SARS-CoV-2 variants, and can aid in the rapid response to any other pandemic-potential pathogens.

SARS-CoV-2 Antibody Level after Homologous and Heterologous Booster Vaccines: an 18-month Longitudinal Observational Cohort Study in Indonesia

Article

Full-text available

Jul 2024
Open Publ Health J

Background Recently, there have been reports of the rise of COVID-19 cases in several sites. The effectiveness of the COVID-19 vaccine was reported elsewhere. There are still questions on how the kinetics of antibody response during relatively long periods, the need for additional doses, and the effect of homologous and heterologous boosters. The study was conducted to analyze the kinetics of antibody response after the primary dose and the third dose of the ChAdOx1 vaccine in individuals previously receiving two doses of the ChAdOx1 [homologous] and CoronaVac [heterologous] COVID-19 vaccines. Methods The study population comprised 52 men and 98 women, divided into CoronaVac Recipients and ChAdOx1 Recipients for the first two doses according to the recommended schedule by the Ministry of Health of Indonesia [MoH].Six months after the second dose, the third dose of ChAdOx1 was administered as a homologous and heterologous booster. COVID-19 antibody levels were measured by the CMIA method before the first dose [time-point or TP1], two weeks after the first dose [TP2], before the second dose [TP3], 1 month after the second dose [TP4], 12 months after the second dose [TP5], and 18 months [TP6] after the second dose administration. Six months after the second dose, the third dose of ChAdOx1 was administered as a homologous and heterologous booster. Along with these, several epidemiological data were collected from subjects on TP1. Results A total of 153 serum samples were collected from subjects who had received the third dose, and the antibody response was measured. On TP1, COVID-19 antibody reactivity [the level was >50 AU/mL] was detected on 100 [66,67%] of subjects, indicating a possible previous exposure to SARS-CoV-2. On TP2, the sharp increase in antibody level was documented in the ChAdOx1 group. However, in the following data during the cohort, the gap was narrowing, and on the TP6, the antibody levels showed no significant difference between groups [p>0.05]. Likewise, no significant differences were shown between groups with or without a history of COVID-19 antibody reactivity on TP1 [p>0.05]. Considering epidemiological characteristics, no significant differences were documented based on sex, age groups, and BMI level. Conclusion This study provides a deeper understanding of the kinetics of antibody levels longitudinally among those with and without previous history of SARS CoV-2 infection, among the recipients of different vaccines, and the recipients of homologous and heterologous boosters. It is necessary to elucidate further in the next study how the level of antibody reflects the neutralizing antibody level as an indicator of protection against the infection risk.

The Integrated Infrared Multifunctional Detection and Tracking System for COVID-19 Protection

Conference Paper

May 2024

Comparative Analysis of Ecological Footprint in Five Cities of India: A Pandemic Analysis

Chapter

Jun 2024

COVID-19, a new respiratory disease identified in December 2019, is one of the most recent risks to human health around the world. The purpose of this research is to examine the effects of COVID-19 on the ecological footprints of five cities across India: Delhi, Bhopal, Bareilly, Betul, and Razole, using the global footprint networks calculator tool. In this comparative analysis, six major factors were employed to examine EF which were examined through food, shelter, transportation, commodities, and services. Further, statistical test - T test and ANOVA analyse the difference ecological footprints in five cities. A total of 15 questions derived from six factors of land use type have been considered for the analysis using primary questionnaires collected via online google forms. The study presents a change in the ecological footprint through exploratory study of different cities with varying population sizes in the times of COVID-19. Results show significant difference in ecological footprint among the cities with maximum variation observed in class I cities like Delhi.

Comparison of Transient and Persistent Adverse Events After COVID-19 Vaccination: A Retrospective Analysis

Article

Full-text available

Jun 2024

Objective: Most reported adverse events following COVID-19 vaccination have been transient. However, persistent adverse events may occur with some frequency. This study aimed to analyze patient background characteristics and trends, with a focus on whether adverse events following COVID-19 vaccination were transient or persistent. Methods: A retrospective study was performed at a single institution in Japan. Patients: The study cohort included 47 patients who presented with symptoms after COVID-19 vaccination between May 2021 and September 2023. The patients were classified into two groups based on the duration of symptoms: transient group, less than four weeks; persistent group, greater than or equal to four weeks. Data on age, sex, body mass index, smoking history, underlying conditions, type of COVID-19 vaccination, number of doses, onset, symptoms, and treatments were collected retrospectively. Results: The median age was 51.0 years and 74.5% were females, with a particularly high proportion of women in their 40s. The use of the bivalent omicron-containing booster vaccine (BA.1) was significantly more common in the persistent group than in the transient group (p = 0.0267). Onset in the transient group was more common after the first vaccination, whereas onset in the persistent group was more common after the second and subsequent vaccinations (p = 0.003). Regarding symptoms, pain was more frequent in the persistent group than in the transient group (60% vs. 13.6%; p = 0.001). Conclusions: This study investigated the presence of persistent symptoms, especially pain, after COVID-19 vaccination. Persistent symptoms were frequently reported after the second vaccination. It should be noted that the study does not negate the usefulness of COVID-19 vaccines.

Exploring COVID-19 Vaccine Intentions, Perceptions, and Uptake Among the Saudi Population

Article

Full-text available

Jun 2024

Background The widespread hesitancy, delays in acceptance, or outright refusal to receive vaccinations, even when readily available, present a notable global challenge. This is particularly pertinent in the context of COVID-19 vaccine hesitancy, where research shows considerable variability in hesitancy rates worldwide. The primary aim of this study is to investigate COVID-19 vaccine intentions among the Saudi population using behavioral theories as a framework. Methodology A descriptive cross-sectional study was conducted in the Kingdom of Saudi Arabia from January 2022 to December 2022. An online self-administered survey was distributed via social media to reach the targeted participants. Both men and women aged >18 years were included, while non-Saudi individuals and people who are less than 18 years old were excluded. A total of 1,139 participants were included. Results The study found that about 96% of respondents were willing to receive a COVID-19 vaccination. Analyzing sociodemographic and COVID-19-related factors with vaccine intention showed that those previously diagnosed with COVID-19 were less likely to refuse vaccination (P = 0.015). Univariate analyses revealed significant differences in the health belief model (HBM) and theory of planned behavior (TPB) dimensions between willing and unwilling participants. Willing individuals perceived greater infection severity (P = 0.543), higher vaccination benefits (P < 0.01), fewer barriers (P < 0.01), more cues to action (P < 0.01), and lower infection prevention self-efficacy (P < 0.01) compared to the unwilling group. TPB dimensions also differed, with willing individuals having more favorable vaccine attitudes (P < 0.01) and stronger vaccination social norms (P < 0.01). A multivariate logistic regression indicated that having COVID-19 increased vaccine willingness likelihood (odds ratio [OR] = 2.11, 95% confidence interval [CI] 1.14-3.91). Perceived barriers (OR = 0.61, 95% CI 0.44-0.85), self-efficacy (OR = 1.96, 95% CI 1.16-3.32) from HBM, and favorable vaccine attitudes (OR = 1.55, 95% CI 1.02-2.35) from TPB were significant predictors of vaccine willingness. Conclusions The TPB highlighted the importance of attitudes and perceived norms in vaccination acceptance, suggesting their value in vaccination promotion strategies. However, further research, including prospective and interventional studies drawing from a wider array of psychological theories, is needed to develop effective interventions for promoting vaccination.

Adverse Effects of COVID-19 Vaccines in the Moroccan Adults and Children during the pandemic

Article

Jun 2024

Exploring the promise of COVID-19 vaccines: A review of preclinical studies

Chapter

Jan 2024

Effectiveness of the vaccine (Covaxin®) on different age groups of people: A pilot study

Article

Apr 2024

Analysis of the Interferon Lambda 3 and 4 Gene Single Nucleotide Polymorphisms and Vaccine Response Against COVID-19

Article

Jan 2023

Introduction Assessing how various COVID-19 vaccines work against SARS-CoV-2 in different individuals is pivotal to planning better management and coping with the pandemic. Single nucleotide polymorphisms (SNPs) are one of the contributing factors to the immune response. This study investigated interferon lambda 3 and 4 (IFNL3/4) gene polymorphism and their association with an individual's immune response after receiving COVID-19 vaccines. Materials and Methods An exploratory laboratory study to identify SNPs rs1297860 and rs368234815 in IFNL3/4 genes in Indonesian who have received two shots of CoronaVac and further evaluate its association with the COVID-19 vaccine response. The immune response was reflected from the serum titres of SARS-CoV-2 IgG (anti-spike IgG level), quantified using the SARS-CoV-2 IgG II Quant assay, where the IFNL3/IFNL4 SNPs identified using polymerase chain reaction restriction fragment length polymorphism. Results From March to August 2021, this study recruited 46 eligible and healthy persons. None of the subjects in this study have the assumed associated genotypes (TT in IFNL3 or DG/DG in IFNL4). There was also no significant difference in the Mean Fold Rise of anti-spike IgG level between individuals with IFNL3 rs12979860 C/T polymorphism (CT genotype) and those with the homozygous common (wild-type) genotype (TT genotype) ( U = 358; P > 0.05). Conclusion The frequency of IFNL3/4 polymorphisms in this study population was low. Furthermore, the IFNL3/4 polymorphisms do not affect immune response (anti-spike IgG level) in individuals receiving two shots of the COVID-19 vaccine in this study.

ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques

Article

Full-text available

Oct 2020
NATURE

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was predominantly Th1, as demonstrated by IgG subclass and cytokine expression profiling. Vaccination with ChAdOx1 nCoV-19 (prime-only and prime-boost regimen) induced a balanced Th1/Th2 humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated animals. However, there was no difference in nasal shedding between vaccinated and control animals. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. Safety, immunogenicity and efficacy of ChAdOx1 nCoV-19 against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial

Article

Full-text available

Jul 2020

Background The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. Methods We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18–55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 10¹⁰ viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. Findings Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493–1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96–317; n=127), and were boosted following a second dose (639 EU, 360–792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R²=0·67 by Marburg VN; p<0·001). Interpretation ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme. Funding UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and the German Center for Infection Research (DZIF), Partner site Gießen-Marburg-Langen.

Multi-Antigenic Virus-like Particle of SARS CoV-2 produced in Saccharomyces cerevisiae as a vaccine candidate

Article

Full-text available

Jul 2020

Spike, Envelope and Membrane proteins from the SARS CoV-2 virus surface coat are important vaccine targets. We hereby report recombinant co-expression of the three proteins (Spike, Envelope and Membrane) in a engineered Saccharomyces cerevisiae platform (D-Crypt™) and their self-assembly as Virus-like particle (VLP). This design as a multi-antigenic VLP for SARS CoV-2 has the potential to be a scalable vaccine candidate. The VLP is confirmed by transmission electron microscopy (TEM) images of the SARS CoV-2, along with supportive HPLC, Dynamic Light Scattering (DLS) and allied analytical data. The images clearly outline the presence of a "Corona" like morphology, and uniform size distribution. Introduction:

Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development

Article

Full-text available

Jun 2020

Significance Since SARS-CoV-2 emerged in China, it has spread rapidly around the world. Effective vaccines and therapeutics for SARS-CoV-2−induced disease (coronavirus disease 2019;COVID-19) are urgently needed. We found that SARS-CoV-2 isolates replicate efficiently in the lungs of Syrian hamsters and cause severe pathological lesions in the lungs of these animals similar to commonly reported imaging features of COVID-19 patients with pneumonia. SARS-CoV-2−infected hamsters mounted neutralizing antibody responses and were protected against rechallenge with SARS-CoV-2. Moreover, passive transfer of convalescent serum to naïve hamsters inhibited virus replication in their lungs. Syrian hamsters are a useful small animal model for the evaluation of vaccines, immunotherapies, and antiviral drugs.

The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19

Article

Full-text available

Jun 2020
J Protein Chem

Francis K. Yoshimoto

The devastating effects of the recent global pandemic (termed COVID-19 for "coronavirus disease 2019") caused by the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) are paramount with new cases and deaths growing at an exponential rate. In order to provide a better understanding of SARS CoV-2, this article will review the proteins found in the SARS CoV-2 that caused this global pandemic.

An Integrated In-Silico Approach to Develop Epitope-Based Peptide Vaccine against SARS-CoV-2

Preprint

Full-text available

May 2020

SARS-CoV-2 has been the talk of the town ever since the beginning of 2020. The pandemic has brought the complete world on a halt. Every country is trying all possible steps to combat the disease ranging from shutting the complete economy of the country to repurposing of drugs and vaccine development. The rapid data analysis and widespread tools, software and databases have made bioinformatics capable of giving new insights to the researchers to deal with the current scenario more efficiently. Vaccinomics, the new emerging field of bioinformatics uses concepts of immunogenetics and immunogenomics with in silico tools to give promising results for wet lab experiments. This approach is highly validated for the designing and development of potent vaccines. The present in-silico study was attempted to identify peptide fragments from spike surface glycoprotein that can be efficiently used for the designing and development of epitope-based vaccine designing approach. Both B-cell and T-cell epitopes are predicted using integrated computational tools. VaxiJen server was used for prediction of protective antigenicity of the protein. NetCTL was studied for analyzing most potent T cell epitopes and its subsequent MHC-I interaction through tools provided by IEDB. 3D structure prediction of peptides and MHC-I alleles (HLA-C*03:03) was further done to carry out docking studies using AutoDock4.0. Various tools from IEDB were used to predict B-cell epitopes on the basis of different essential parameters like surface accessibility, beta turns and many more. Based on results interpretation, the peptide sequence from 1138-1145 amino acid and sequence WTAGAAAYY and YDPLQPEL were obtained as a potential B-cell epitope and T-cell epitope respectively. This in-silico study will help us to identify novel epitope-based peptide vaccine target in spike protein of SARS-CoV-2. Further, in-vitro and in-vivo study needed to validate the findings.

Immunogenicity of a DNA vaccine candidate for COVID-19

Article

Full-text available

May 2020

The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study. There is currently no licensed SARS-CoV-2 vaccine. Here, the authors generate an optimized DNA vaccine candidate encoding the SARS-CoV-2 spike antigen, demonstrating induction of specific T cells and neutralizing antibody responses in mice and guinea pigs. These initial results support further development of this vaccine candidate.

Multi-Antigenic Virus-like Particle of SARS CoV-2 produced in Saccharomyces cerevisiae as a vaccine candidate

Preprint

Full-text available

May 2020

Spike, Envelope and Membrane proteins from the SARS CoV-2 virus surface coat are important vaccine targets. We hereby report recombinant co-expression of the three proteins (Spike, Envelope and Membrane) in a engineered Saccharomyces cerevisiae platform (D-Crypt™) and their self-assembly as Virus-like particle (VLP). This design as a multi-antigenic VLP for SARS CoV-2 has the potential to be a scalable vaccine candidate. The VLP is confirmed by transmission electron microscopy (TEM) images of the SARS CoV-2, along with supportive HPLC, Dynamic Light Scattering (DLS) and allied analytical data. The images clearly outline the presence of a Corona like morphology, and uniform size distribution.

ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

Preprint

Full-text available

May 2020

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.

Emergence of genomic diversity and recurrent mutations in SARS-CoV-2

Article

Full-text available

May 2020
INFECT GENET EVOL

SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 52,020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.

Expansion of Neutrophils and Classical and Nonclassical Monocytes as a Hallmark in Relapsing-Remitting Multiple Sclerosis

Article

Full-text available

Apr 2020

Neutrophils and monocytes encompassing the classical, intermediate, and nonclassical population constitute the majority of circulating myeloid cells in humans and represent the first line of innate immune defense. As such, changes in their relative and absolute amounts serve as sensitive markers of diverse inflammatory conditions. Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, causing demyelination and axonal loss, affecting various neuron functions and often causing irreversible neurological disability. MS disease course is individually highly heterogeneous but can be classified as progressive (PMS) or relapsing-remitting (RRMS). Each MS course type may be further characterized as active or inactive, depending on the recent disability progression and/or current relapses. Data on specific alterations of the myeloid compartment in association with MS disease course are scarce and conflicting. In the current study, we systematically immunophenotyped blood myeloid leukocytes by flow cytometry in 15 healthy and 65 MS subjects. We found a highly significant expansion of granulocytes, CD15⁺ neutrophils, and classical and nonclassical monocytes in inactive RRMS (RRMSi) with concomitant shrinkage of the lymphocyte compartment, which did not correlate with biochemical readouts of systemic inflammation. Each of these leukocyte populations and the combined myeloid signature accurately differentiated RRMSi from other MS forms. Additionally, nonclassical monocyte proportions were particularly elevated in RRMSi individuals receiving disease-modifying therapy (DMT), such as natalizumab. Our results suggest that flow cytometry-based myeloid cell immunophenotyping in MS may help to identify RRMSi earlier and facilitate monitoring of DMT response.

Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea

Article

Full-text available

Apr 2020
J KOREAN MED SCI

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.

A Review of SARS-CoV-2 and the Ongoing Clinical Trials

Article

Full-text available

Apr 2020
INT J MOL SCI

The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) in Wuhan, China, which rapidly grew into a global pandemic, marked the third introduction of a virulent coronavirus into the human society, affecting not only the healthcare system, but also the global economy. Although our understanding of coronaviruses has undergone a huge leap after two precedents, the effective approaches to treatment and epidemiological control are still lacking. In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initial Wuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including favipiravir, a broad-spectrum antiviral drug that interferes with the viral replication, and hydroxychloroquine, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis.

The COVID-19 vaccine development landscape

Article

Full-text available

Apr 2020

Role of Nonstructural Proteins in the Pathogenesis of SARS-CoV-2

Article

Full-text available

Apr 2020

We read with great interest the study authored by Angeletti et al. regarding the role of nonstructural proteins nsp2 and nsp3 in the pathogenesis of COVID‐19¹. COVID‐19 emerged in December 2019 in Wuhan City, Hubei Province, China and is caused by a novel viral variant belonging to the viral variant belonging to the Severe acute respiratory syndrome‐related coronavirus (SARS‐rCoV) species of subgenus Sarbecovirus, genus Betacoronavirus, family Coronaviridae and named SARS‐CoV‐2². This article is protected by copyright. All rights reserved.

Effectiveness of convalescent plasma therapy in severe COVID-19 patients

Article

Full-text available

Apr 2020

Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 10 ⁹ /L vs. 0.76 × 10 ⁹ /L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.

Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development

Article

Full-text available

Apr 2020

Background Coronaviruses pose a serious threat to global health as evidenced by Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19. SARS Coronavirus (SARS-CoV), MERS Coronavirus (MERS-CoV), and the novel coronavirus, previously dubbed 2019-nCoV, and now officially named SARS-CoV-2, are the causative agents of the SARS, MERS, and COVID-19 disease outbreaks, respectively. Safe vaccines that rapidly induce potent and long-lasting virus-specific immune responses against these infectious agents are urgently needed. The coronavirus spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target for vaccines for the prevention of coronavirus infection. Methods We first generated codon optimized MERS-S1 subunit vaccines fused with a foldon trimerization domain to mimic the native viral structure. In variant constructs, we engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric design. We comprehensively tested the pre-clinical immunogenicity of MERS-CoV vaccines in mice when delivered subcutaneously by traditional needle injection, or intracutaneously by dissolving microneedle arrays (MNAs) by evaluating virus specific IgG antibodies in the serum of vaccinated mice by ELISA and using virus neutralization assays. Driven by the urgent need for COVID-19 vaccines, we utilized this strategy to rapidly develop MNA SARS-CoV-2 subunit vaccines and tested their pre-clinical immunogenicity in vivo by exploiting our substantial experience with MNA MERS-CoV vaccines. Findings Here we describe the development of MNA delivered MERS-CoV vaccines and their pre-clinical immunogenicity. Specifically, MNA delivered MERS-S1 subunit vaccines elicited strong and long-lasting antigen-specific antibody responses. Building on our ongoing efforts to develop MERS-CoV vaccines, promising immunogenicity of MNA-delivered MERS-CoV vaccines, and our experience with MNA fabrication and delivery, including clinical trials, we rapidly designed and produced clinically-translatable MNA SARS-CoV-2 subunit vaccines within 4 weeks of the identification of the SARS-CoV-2 S1 sequence. Most importantly, these MNA delivered SARS-CoV-2 S1 subunit vaccines elicited potent antigen-specific antibody responses that were evident beginning 2 weeks after immunization. Interpretation MNA delivery of coronaviruses-S1 subunit vaccines is a promising immunization strategy against coronavirus infection. Progressive scientific and technological efforts enable quicker responses to emerging pandemics. Our ongoing efforts to develop MNA-MERS-S1 subunit vaccines enabled us to rapidly design and produce MNA SARS-CoV-2 subunit vaccines capable of inducing potent virus-specific antibody responses. Collectively, our results support the clinical development of MNA delivered recombinant protein subunit vaccines against SARS, MERS, COVID-19, and other emerging infectious diseases.

Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19-related respiratory failure: a case report

Article

Full-text available

Apr 2020

Epidemiology, virology, and clinical features of severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2; Coronavirus Disease-19)

Article

Full-text available

Apr 2020

Su Eun Park

A cluster of severe pneumonia of unknown etiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was isolated from lower respiratory tract sample as the causative agent. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 rapidly spread into at least 114 countries and killed more than 4,000 people by March 11 2020. WHO officially declared COVID-19 a pandemic on March 11, 2020. There have been two novel coronavirus outbreaks in the past two decades. The 2002-2003 outbreak of severe acute respiratory syndrome (SARS) in 2002-2003 caused by SARS-CoV had a case fatality rate of around 10% (8,098 confirmed cases and 774 death), while Middle East respiratory syndrome (MERS) caused by MERS-CoV killed 861 people out of a total 2,502 confirmed cases between 2012 and 2019. The purpose of this review is to summarize known-to-date information about SARS-CoV-2, transmission of SARS-CoV-2, and clinical features.

Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure

Article

Full-text available

Mar 2020
J INFECT DIS

Controlled human challenge trials of SARS-CoV-2 vaccine candidates could accelerate the testing and potential rollout of efficacious vaccines. By replacing conventional Phase 3 testing of vaccine candidates, such trials may subtract many months from the licensure process, making efficacious vaccines available more quickly. Obviously, challenging volunteers with this live virus risks inducing severe disease and possibly even death. However, we argue that such studies, by accelerating vaccine evaluation, could reduce the global burden of coronavirus-related mortality and morbidity. Volunteers in such studies could autonomously authorize the risks to themselves, and their net risk could be acceptable if participants comprise healthy young adults, who are at relatively low risk of serious disease following natural infection, they have a high baseline risk of natural infection, and during the trial they receive frequent monitoring and, following any infection, the best available care.

Treatment With Convalescent Plasma for Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Article

Full-text available

Mar 2020

As of March 24, 2020, novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for 379,661 infection cases with 16,428 deaths globally and the number is still increasing rapidly. Herein, we presented four critically ill patients with SARS-CoV-2 infection who received supportive care and convalescent plasma. Although all the four patients recovered from SARS-CoV-2 infection eventually, randomized trials are needed to eliminate the effect of other treatments and investigate the safety and efficacy of convalescent plasma therapy.

Treatment of 5 Critically Ill Patients with COVID-19 with Convalescent Plasma

Article

Full-text available

Mar 2020

Importance Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments. Objective To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design, Setting, and Participants Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; Pao2/Fio2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion. Exposures Patients received transfusion with convalescent plasma with a SARS-CoV-2–specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission. Main Outcomes and Measures Changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), Pao2/Fio2, viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion. Results All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2–specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion. Conclusions and Relevance In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.

Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV

Article

Full-text available

Mar 2020

Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2. SARS-CoV-2 has spread globally. Here, the authors characterize the entry pathway of SARS-CoV-2, show that the SARS-CoV-2 spike protein is less stable than that of SARS-CoV, and show limited cross-neutralization activities between SARS-CoV and SARS-CoV-2 sera.

Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine

Article

Full-text available

Mar 2020

The outbreak of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). The CoV spike (S) protein plays the most important roles in viral attachment, fusion and entry, and serves as a target for development of antibodies, entry inhibitors and vaccines. Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and, hence, attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells, thus inhibiting their infection to host cells. SARS-CoV RBD-specific antibodies could cross-react with SARS-CoV-2 RBD protein, and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection.

Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody

Article

Full-text available

Feb 2020

The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 11,900 laboratory-confirmed human infections, including 259 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. These results suggest that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.

Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases

Article

Full-text available

Mar 2020

Since the outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, this disease has spread rapidly around the globe. Considering the potential threat of a pandemic, scientists and physicians have been racing to understand this new virus and the pathophysiology of this disease to uncover possible treatment regimens and discover effective therapeutic agents and vaccines. To support the current research and development, CAS has produced a special report to provide an overview of published scientific information with an emphasis on patents in the CAS content collection. It highlights antiviral strategies involving small molecules and biologics targeting complex molecular interactions involved in coronavirus infection and replication. The drug-repurposing effort documented herein focuses primarily on agents known to be effective against other RNA viruses including SARS-CoV and MERS-CoV. The patent analysis of coronavirus-related biologics includes therapeutic antibodies, cytokines, and nucleic acid-based therapies targeting virus gene expression as well as various types of vaccines. More than 500 patents disclose methodologies of these four biologics with the potential for treating and preventing coronavirus infections, which may be applicable to COVID-19. The information included in this report provides a strong intellectual groundwork for the ongoing development of therapeutic agents and vaccines.

The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines

Article

Full-text available

Dec 2020

The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern. However, no specific antiviral treatments or vaccines are available yet. This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2.

Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses

Article

Full-text available

Feb 2020

Seven coronaviruses (CoVs) have been isolated from humans so far. Among them, three emerging pathogenic CoVs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and a newly identified CoV (2019-nCoV), once caused or continue to cause severe infections in humans, posing significant threats to global public health. SARS-CoV infection in humans (with about 10% case fatality rate) was first reported from China in 2002, while MERS-CoV infection in humans (with about 34.4% case fatality rate) was first reported from Saudi Arabia in June 2012. 2019-nCoV was first reported from China in December 2019, and is currently infecting more than 70000 people (with about 2.7% case fatality rate). Both SARS-CoV and MERS-CoV are zoonotic viruses, using bats as their natural reservoirs, and then transmitting through intermediate hosts, leading to human infections. Nevertheless, the intermediate host for 2019-nCoV is still under investigation and the vaccines against this new CoV have not been available. Although a variety of vaccines have been developed against infections of SARS-CoV and MERS-CoV, none of them has been approved for use in humans. In this review, we have described the structure and function of key proteins of emerging human CoVs, overviewed the current vaccine types to be developed against SARS-CoV and MERS-CoV, and summarized recent advances in subunit vaccines against these two pathogenic human CoVs. These subunit vaccines are introduced on the basis of full-length spike (S) protein, receptor-binding domain (RBD), non-RBD S protein fragments, and non-S structural proteins, and the potential factors affecting these subunit vaccines are also illustrated. Overall, this review will be helpful for rapid design and development of vaccines against the new 2019-nCoV and any future CoVs with pandemic potential. This review was written for the topic of Antivirals for Emerging Viruses: Vaccines and Therapeutics in the Virology section of Frontiers in Microbiology.

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Article

Full-text available

Feb 2020

Structure of the nCoV trimeric spike The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. Science , this issue p. 1260

COVID-19, an emerging coronavirus infection: Advances and prospects in designing and developing vaccines, immunotherapeutics and therapeutics

Article

Full-text available

Feb 2020

The novel coronavirus infection (COVID-19 or Coronavirus disease 2019) that emerged from Wuhan, Hubei province of China has now spread to several countries across the world. Efforts have been made to develop vaccines against human coronavirus (CoV) infections in the past decades, however till date no licensed antiviral treatment or vaccine exists for MERS and SARS CoVs. Most of the efforts for developing CoVs vaccines and drugs target the spike glycoprotein or S protein, the major inducer of neutralizing antibodies. Although a few have shown proven efficacy in the in vitro studies, not many have undergone randomized animal or human trials, hence may have limited use to counter COVID-19. This article highlights the recent ongoing advances in designing vaccines and therapeutics to counter COVID-19, while also focusing such experiences and advances as made with earlier SARS and MERS-CoVs; which altogether could pave ways in the right direction to halt this emerging virus.

The Pathogenicity of 2019 Novel Coronavirus in hACE2 Transgenic Mice

Preprint

Full-text available

Feb 2020

2019-nCoV caused pneumonia cases in China has become a public health emergency of international concern (PHEIC). The first priority for prevention and treatment of the disease is to find the pathogenicity of 2019-nCoV in vivo. Weight loss and virus replication were detected in infected-hACE2 mice. The typical histopathology was interstitial pneumonia with significant inflammatory cells infiltration around the bronchioles and blood vessels, and viral antigens were observed in bronchial epithelial cells and alveolar epithelial cells. The phenomenon was not found in wild type mice infected with 2019-nCoV and the mock-infected hACE2 mice. The pathogenicity of 2019-nCoV in hACE2 mice was clarified and the Koch's postulates was fulfilled as well, and the model may facilitate the development of therapeutics and vaccines against 2019-nCoV.

Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China

Article

Full-text available

Feb 2020
CELL HOST MICROBE

An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.

Immunoinformatics-aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019-nCoV

Article

Full-text available

Feb 2020

The 2019 novel coronavirus (2019‐nCoV) outbreak has caused a large number of deaths with thousands of confirmed cases worldwide, especially in East Asia. This study took an immunoinformatics approach to identify significant cytotoxic T lymphocyte (CTL) and B cell epitopes in the 2019‐nCoV surface glycoprotein. Also, interactions between identified CTL epitopes and their corresponding major histocompatibility complex (MHC) class I supertype representatives prevalent in China were studied by molecular dynamics simulations. We identified five CTL epitopes, three sequential B cell epitopes and five discontinuous B cell epitopes in the viral surface glycoprotein. Also, during simulations, the CTL epitopes were observed to be binding MHC class I peptide‐binding grooves via multiple contacts, with continuous hydrogen bonds and salt bridge anchors, indicating their potential in generating immune responses. Some of these identified epitopes can be potential candidates for the development of 2019‐nCoV vaccines. Highlights • Five CTL epitopes and eight B cell epitopes were computationally identified. • Epitope‐MHC‐I complexes were studied by molecular dynamics simulation. • Persistent H‐bonds and salt bridges were observed between epitopes and MHC‐I. • The identified epitopes can be a promising foundation for vaccine development.

An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies

Article

Full-text available

Jan 2020

Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS

Article

Full-text available

Mar 2020
J VIROL

The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.

Return of the Coronavirus: 2019-nCoV

Article

Full-text available

Jan 2020

The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus.

Advances in mRNA Vaccines for Infectious Diseases

Article

Full-text available

Mar 2019

During the last two decades, there has been broad interest in RNA-based technologies for the development of prophylactic and therapeutic vaccines. Preclinical and clinical trials have shown that mRNA vaccines provide a safe and long-lasting immune response in animal models and humans. In this review, we summarize current research progress on mRNA vaccines, which have the potential to be quick-manufactured and to become powerful tools against infectious disease and we highlight the bright future of their design and applications.

Complexity of the Basic Reproduction Number (R0)

Article

Full-text available

Jan 2019

The basic reproduction number (R0), also called the basic reproduction ratio or rate or the basic reproductive rate, is an epidemiologic metric used to describe the contagiousness or transmissibility of infectious agents. R0 is affected by numerous biological, sociobehavioral, and environmental factors that govern pathogen transmission and, therefore, is usually estimated with various types of complex mathematical models, which make R0 easily misrepresented, misinterpreted, and misapplied. R0 is not a biological constant for a pathogen, a rate over time, or a measure of disease severity, and R0 cannot be modified through vaccination campaigns. R0 is rarely measured directly, and modeled R0 values are dependent on model structures and assumptions. Some R0 values reported in the scientific literature are likely obsolete. R0 must be estimated, reported, and applied with great caution because this basic metric is far from simple.

An Integrated In-Silico Approach to Develop Epitope-Based Peptide Vaccine against SARS-CoV-2

Article

Feb 2021

Background SARS-CoV-2 has been the talk of the town ever since the beginning of 2020. Every country is trying all possible steps to combat the disease ranging from shutting the complete economy of the country to the repurposing of drugs and vaccine development. The rapid data analysis and widespread tools have made bioinformatics capable of giving new insights to deal with the current scenario more efficiently through an emerging field, Vaccinomics. Objective The present in-silico study was attempted to identify peptide fragments from spike surface glycoprotein of SARS-CoV-2 that can be efficiently used for the development of an epitope-based vaccine designing approach. Methodology The epitopes of B and T-cell are predicted using integrated computational tools. VaxiJen server, NetCTL, and IEDB tools were used to study, analyze, and predict potent T-cell epitopes, its subsequent MHC-I interactions, and B-cell epitopes. The 3D structure prediction of peptides and MHC-I alleles (HLA-C*03:03) was further done using AutoDock4.0. Result Based on result interpretation, the peptide sequence from 1138-1145 amino acid and sequence WTAGAAAYY and YDPLQPEL were obtained as potential B-cell and T-cell epitopes respectively. Conclusion The peptide sequence WTAGAAAYY and the amino acid sequence from 1138-1145 of the spike protein of SARS-CoV-2 can be used as a probable B-cell epitope candidate. Also, the amino acid sequence YDPLQPEL can be used as a potent T-cell epitope. This in-silico study will help us to identify novel epitope-based peptide vaccine targets in the spike protein of SARS-CoV-2. Further, the in-vitro and in-vivo study needed to validate the findings.

Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial

Article

Jul 2020

Background This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study. Methods This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 10¹¹ viral particles per mL or 5 × 10¹⁰ viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389. Findings 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 10¹¹ viral particles n=253; 5 × 10¹⁰ viral particles n=129) or placebo (n=126). In the 1 × 10¹¹ and 5 × 10¹⁰ viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2–749·2) and 571·0 (467·6–697·3), with seroconversion rates at 96% (95% CI 93–98) and 97% (92–99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8–22·7) and 18·3 (14·4–23·3) in participants receiving 1 × 10¹¹ and 5 × 10¹⁰ viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85–93) of 253 and 113 (88%, 81–92) of 129 participants in the 1 × 10¹¹ and 5 × 10¹⁰ viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 10¹¹ and 5 × 10¹⁰ viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 10¹¹ viral particles dose group and one (1%) participant in the 5 × 10¹⁰ viral particles dose group. No serious adverse reactions were documented. Interpretation The Ad5-vectored COVID-19 vaccine at 5 × 10¹⁰ viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation. Funding National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.

An mRNA vaccine against SARS-COV-2 — Preliminary report

Article

Jul 2020

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. Methods We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group. Results After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti–S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events. Conclusions The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).

Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial

Article

May 2020

Background A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Methods We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 10¹⁰, 1 × 10¹¹, and 1·5 × 10¹¹ viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. Findings Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. Interpretation The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. Funding National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.

Rapid COVID-19 vaccine development

Article

May 2020

Barney S. Graham

Finding the fastest pathway to vaccine availability includes the avoidance of safety pitfalls

The epidemiology, diagnosis and treatment of COVID-19

Article

Mar 2020
INT J ANTIMICROB AG

In December 2019, the outbreak of the 2019 novel coronavirus disease (COVID-19) in China spread worldwide, becoming an emergency of major international concern. SARS-CoV-2 infection causes clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus. Human-to-human transmission has been described with incubation times between 2-14 days, facilitating its spread via droplets, contaminated hands or surfaces. Early diagnosis, quarantine, and supportive treatments are essential to cure patients. We therefore reviewed the literature on all available information about the epidemiology, diagnosis, isolation and treatments of COVID-19. Treatments, including antiviral agents, chloroquine and hydroxychloroquine, corticosteroids, antibodies, convalescent plasma transfusion and vaccines, will be discussed in this article. Additionally, registered trials about treatment were listed to develop approaches for the current urgent demand for therapy.

The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application

Article

Mar 2020
ANN INTERN MED

Background: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. Objective: To estimate the length of the incubation period of COVID-19 and describe its public health implications. Design: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. Setting: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. Participants: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. Measurements: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. Results: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. Limitation: Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases. Conclusion: This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases. Primary funding source: U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation.

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Article

Mar 2020
CELL

The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

Subcutaneous nodules following immunization in children; in Victoria, Australia from 2007 to 2016

Article

Mar 2020
VACCINE

Background Subcutaneous nodules are a rare adverse event following immunization (AEFI). We aimed to describe nodules at the injection site reported to SAEFVIC (Surveillance of Adverse Events Following Vaccination in the Community) using the Brighton Collaboration Case Definition (BCCD), management and recurrence following subsequent immunizations. Method We assessed 58 cases (<18 years of age) of ‘nodule at injection site’ reported to SAEFVIC, Melbourne, Australia, between May 2007 and June 2016. Case details were analyzed from records and phone interview follow-up. The Australian Immunization Registry was reviewed for immunization status. Results 71% (41/58 reported cases) were consistent with the BCCD for subcutaneous nodule, 14% (8 cases) were ‘possible subcutaneous nodules’, 10% (6 cases) were nodules associated with BCG immunization and 5% (3 cases) were attributable to an alternative diagnosis. The median age at immunization was 12 months, (range 1 month–12 years); 54% male (22/41 cases). 17% (7 cases) had multiple nodules. Nodules were associated with immunizations containing aluminum (74%, 36/49 nodules), no aluminum (8%, 4 nodules) and unknown (18%, 9 nodules). Most cases developed symptoms within 3 days post-immunization (59%, 24 cases) and in the thigh (59%, 29 nodules). Pruritus was associated in 41% (17 cases). Around 1/3 (34%) of nodules resolved 6 months post immunization, 2/3 (68%) by 12 months, however 1/4 (24%) remained persistent for >24 months. 5 cases had prior nodules and 1 case had recurrence with subsequent immunization. 83% (34 cases) were fully immunized for age at follow-up. Conclusion Subcutaneous nodules at the injection site may occur following a wide range of vaccines, including vaccines without aluminum. All cases require careful review and where possible, specialist management and to support subsequent immunizations.

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Article

Mar 2020

The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

Article

Feb 2020

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

Article

Jan 2020

Background: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding: National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.