Article

Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross‐species transmission from snake to human

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019‐nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many initial patients were exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To investigate possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on the 2019‐nCoV sequence. Results obtained from our analyses suggest that the 2019‐nCoV may appear to be a recombinant virus between the bat coronavirus and an origin‐unknown coronavirus. The recombination may occurred within the viral spike glycoprotein, which recognizes a cell surface receptor. Additionally, our findings suggest that 2019‐nCoV has most similar genetic information with bat coronovirus and most similar codon usage bias with snake. Taken together, our results suggest that homologous recombination may occur and contribute to the 2019‐nCoV cross‐species transmission. Research Highlights • Taken together, our results suggest that homologous recombination may occur and contribute to the 2019‐nCoV cross‐species transmission.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Many medications have been used for SARS-CoV-2 treatment. However, appropriate drugs remain undiscovered; thus, indefinite drugs are being administered to patients, while suitable medications and vaccines are being explored [8,9]. Hydroxychloroquine is an antimalarial drug that inhibits heme detoxification when administered to parasitic patients. ...
... In the search for novel HIV-1 non-nucleoside reverse transcriptase inhibitors (NNR-TIs), phenylamino-phenoxy-quinoline derivatives have been synthesized from a combination of the pharmacophore templates of nevirapine (NVP), efavirenz (EFV), and rilpivirine (TMC278) [22,23]. These compounds can be divided into two groups, 4,6disubstituted quinoline (1-4) and 2,4-disubstituted quinoline (5)(6)(7)(8), and have been evaluated for their inhibitory effect on HIV-1 reverse transcriptase. A previous study indicated that 2-phenylamino-4-phenoxy-quinoline derivatives exhibited similar percentage inhibitory activity to that of NVP. ...
... Furthermore, the total polar surface area (TPSA) should be less than 140 Å 2 , and the number of rotatable bonds should be less than 10 [27,28]. According to pharmacoki-netic studies of compounds, only hydroxychloroquine, PF-07321332, and compounds (1)(2)(3)(4)(5)(6)(7)(8) correspond with Lipinski's rule of five, together with their number of rotatable bonds being less than 10 (except PF-07321332) and TPSA less than 140 Å 2 , as shown in Table 1. Therefore, hydroxychloroquine, PF-07321332, and phenylamino-phenoxy-quinoline derivatives (1)(2)(3)(4)(5)(6)(7)(8) are in accordance with Lipinski's rule of five and are appropriate candidate drugs against SARS-CoV-2 main protease. ...
Article
Full-text available
In the search for new anti-HIV-1 agents, two forms of phenylamino-phenoxy-quinoline derivatives have been synthesized, namely, 2-phenylamino-4-phenoxy-quinoline and 6-phenylamino-4-phenoxy-quinoline. In this study, the binding interactions of phenylamino-phenoxy-quinoline derivatives and six commercially available drugs (hydroxychloroquine, ritonavir, remdesivir, S-217622, N3, and PF-07321332) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) were investigated using molecular docking and the ONIOM method. The molecular docking showed the hydrogen bonding and hydrophobic interactions of all the compounds in the pocket of SARS-CoV-2 main protease (Mpro), which plays an important role for the division and proliferation of the virus into the cell. The binding free energy values between the ligands and Mpro ranged from −7.06 to −10.61 kcal/mol. The molecular docking and ONIOM results suggested that 4-(2′,6′-dimethyl-4′-cyanophenoxy)-2-(4″-cyanophenyl)-aminoquinoline and 4-(4′-cyanophenoxy)-2-(4″-cyanophenyl)-aminoquinoline have low binding energy values and appropriate molecular properties; moreover, both compounds could bind to Mpro via hydrogen bonding and Pi-Pi stacking interactions with amino acid residues, namely, HIS41, GLU166, and GLN192. These amino acids are related to the proteolytic cleavage process of the catalytic triad mechanisms. Therefore, this study provides important information for further studies on synthetic quinoline derivatives as antiviral candidates in the treatment of SARS-CoV-2.
... The viruses cause cold in humans including CoVs and CoVs are also responsible for high mortality rate. SARS-CoV and MERS-CoV were identified in animal sources [39]. 31 st December 2019, a novel strain of CoV was identified named as SARS-CoV-2. ...
... CTL epitopes have been discovered to develop a peptide vaccine against HLA-B protein. The epitope-based vaccines were being used to target SARS-CoV-2 structural proteins, and CTL epitopes of the target proteins were anticipated to boost the immune response of host [39]. A non-structural protein (PDB 6M2N) was selected for epitope based vaccine design as it has significant rle in the replication of SARS-CoV-2. ...
Article
Full-text available
Coronaviruses (CoVs) are positive-stranded RNA viruses with short clubs on their edges. CoVs are pathogenic viruses that infect several animals and plant organisms, as well as humans (lethal respiratory dysfunctions). A noval strain of CoV has been reported and named as SARS-CoV-2. Numerous COVID-19 cases were being reported all over the World. COVID-19 and has a high mortality rate. In the present study, immunoinformatics techniques were utilized to predict the antigenic epitopes against 3C like protein. B-cell epitopes and Cytotoxic T-lymphocyte (CTL) were designed computationally against SARS-CoV-2. Multiple Sequence Alignment (MSA) of seven complete strains (HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2) was performed to elucidate the binding domain and interacting residues. MHC-I binding epitopes were evaluated by analyzing the binding affinity of the top-ranked peptides having HLA molecule. By utilizing the docked complexes of CTL epitopes with antigenic sites, the binding relationship and affinity of top-ranked predicted peptides with the MHC-I HLA protein were investigated. The molecular docking analyses were conducted on the ZINC database library and twelve compounds having least binding energy were scrutinized. In conclusion, twelve CTL epitopes (GTDLEGNFY, TVNVLAWLY, GSVGFNIDY, SEDMLNPNY, LSQTGIAV, VLDMCASLK, LTQDHVDIL, TTLNDFNLV, CTSEDMLNP, TTITVNVLA, YNGSPSGVY, and SMQNCVLKL) were identified against SARS-CoV-2.
... The first antivirals were developed against herpes viruses in the 1960s and were based on a strategy of antimetabolites-nonphysiological components of nucleic acids. Note that the same strategy leads to very similar molecules, which are also still used in anticancer therapy (Bryan-Marrugo et al., 2015;Bule, Khan, & Niaz, 2019;Ji & Li, 2020;Pardi & Weissman, 2020;Richman & Nathanson, 2016;Roche et al., 2019). ...
... The current clinical diagnosis of the new SARS-CoV-2 infection is based on real-time PCR and serological analysis. Evidence dictates that the new nSARS-CoV-2 infections emerge with symptoms appearing 5-14 days after exposure to virus, yet in many cases, patients remain asymptomatic (Ji, Wang, Zhao, Zai, & Li, 2020). The more significant challenge is the lack of adequate diagnosis in the early stage of new nSARS-CoV-2 infection and their subsequent management. ...
Chapter
Full-text available
Materials at nanometric dimensions offer novel abilities with different properties which cannot be observed with the same material in bulk form. Nanoscience typically refers to the study of nanomaterials, their properties, and related phenomena (Mulvaney, 2015). Nanotechnology refers to the moderation, advancement, and application of atomic or molecular structures at the base of one dimension in the nanoscale range (1–1000nm) to produce devices and products. These particles offer varying shapes, morphologies, compositions, dimensions, or surface characteristics (Fig. 1) (Li, Xiao, Chen, & Huang, 2021; Singh, Misra, Mohanty, & Sahoo, 2020). A diverse range of nanosized particles of both biological and abiological origin includes lipid nanoparticles, nanoemulsions, biodegradable polymers, dendrimers, carbon nanoparticles, exosomes, and viral coats for the potential protected delivery of vaccine components (Chintagunta, Krishna, & Nalluru, 2021; Nasrollahzadeh, Sajjadi, Soufi, Iravani, & Varma, 2020). Nanotechnology involved the manipulation of these materials and emerged as a powerful tool in multiple ways to support the fight against various emerging infections (Chintagunta et al., 2021). In the context of the current pandemic setoff by SARS COV-2, population immunization on a large scale is regarded as a foremost priority for the public health concern.
... The first antivirals were developed against herpes viruses in the 1960s and were based on a strategy of antimetabolites-nonphysiological components of nucleic acids. Note that the same strategy leads to very similar molecules, which are also still used in anticancer therapy (Bryan-Marrugo et al., 2015;Bule, Khan, & Niaz, 2019;Ji & Li, 2020;Pardi & Weissman, 2020;Richman & Nathanson, 2016;Roche et al., 2019). ...
... The current clinical diagnosis of the new SARS-CoV-2 infection is based on real-time PCR and serological analysis. Evidence dictates that the new nSARS-CoV-2 infections emerge with symptoms appearing 5-14 days after exposure to virus, yet in many cases, patients remain asymptomatic (Ji, Wang, Zhao, Zai, & Li, 2020). The more significant challenge is the lack of adequate diagnosis in the early stage of new nSARS-CoV-2 infection and their subsequent management. ...
Chapter
Full-text available
Viral infections are inevitable, and since ancient times, there are an increasing number of records of such outbreaks affecting a million lives (Bauerfeind, von Graevenitz, Kimmig, et al., 2016). In 1918–20, the deadly viral outbreak (Spanish Flu) in human history affected two-third of the human population with a high mortality rate. In the 21st century, there has been a subsequent viral outbreak, including SARS in 2002 in China, MERS in the Middle East, NiPAH in India (2009), Ebola, and H1N1 (also new variants). The rise in such viral outbreaks affected human lives and posed challenges to the existing health-care system (Morens & Taubenberger, 2018; Tong, 2006). In the last two decades of the 21st century, more than ten viral outbreaks have been reported worldwide. More than 2.5 million deaths in the case of novel SARS-CoV-2 have been reported; however, the pandemic is not over yet. New strains of the novel SARS-CoV-2 are cautiously emerging in different geographical areas with varying infection and fatality rates (Junejo, Ozaslan, Safdar, et al., 2020). The coronavirus is most common viral infection to humans after H1N1 and its novel variants. All these viruses primarily target the lower and upper respiratory tract causing acute respiratory distress syndrome. The novel SARS-CoV-2 is the prime causative agent for the deadly COVID-19. Based on the recurrent viral outbreaks in the last two decades, it has been hypothesized that human-animal interaction is the prime cause for viral transmission from wild animals to humans (Rabaan et al., 2020).
... Initially, the infected individuals were those who visited the seafood market or consumed foods of animal origin probably infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Later, a more in-depth analysis through contact tracing of patients positive for COVID-19 revealed that several individuals with no history of trips to the seafood market also tested positive for the disease, indicating the possibility of transmission from person to person (Chan J. F. et al., 2020;Ji et al., 2020). ...
... The transmissibility of SARS-CoV-2 is not known with precision. It is believed that the ingestion of infected animals as a food source is the main cause of zoonotic transmission (Ji et al., 2020). As SARS-CoV-2 is highly similar to SARS-CoV, bats could be the host of the new coronavirus. ...
Article
Full-text available
The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the death of millions of people worldwide and thousands more infected individuals developed sequelae due to the disease of the new coronavirus of 2019 (COVID-19). The development of several studies has contributed to the knowledge about the evolution of SARS-CoV2 infection and the disease to more severe forms. Despite this information being debated in the scientific literature, many mechanisms still need to be better understood in order to control the spread of the virus and treat clinical cases of COVID-19. In this article, we carried out an extensive literature review in order to bring together, in a single article, the biological, social, genetic, diagnostic, therapeutic, immunization, and even socioeconomic aspects that impact the SAR-CoV-2 pandemic. This information gathered in this article will enable a broad and consistent reading of the main aspects related to the current pandemic.
... Coronavirus disease 2019 , caused by infection with the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2), presentsan urgent threat and a paramount to global health and has caused a worldwide pandemic (1)(2)(3)(4)(5). As of March25, 2022, there were 476,374,234 confirmed cases, of them6,108,976cases died worldwide (6). ...
... As of March25, 2022, there were 476,374,234 confirmed cases, of them6,108,976cases died worldwide (6). COVID-19generally had a good prognosis (1)(2)(3)(4)(5), but a poor prognosis was found in those of old age, high number and specific comorbidities, and a rapid disease progression (7)(8)(9)(10)(11)(12).The majority of COVID-19 patients who have died had pre-existing conditions, including hypertension, cardiovascular disease, diabetes, and cancer (10,13). ...
Article
Full-text available
Background Cellular immunodeficiency and comorbidities are common in COVID-19 patients.AimThe purpose of this study was to investigate comorbidities impacting on the cellular immunity in COVID-19 patients.Methods The research objects included 55 healthy controls and 718 COVID-19 patients who divided into the control group and the COVID-19 group, respectively. Those in the COVID-19 group were divided into subgroups on the basis of the number and types of comorbidities present. Lymphocyte itself and its subsets were compared between the control group and the COVID-19 group, the groups with comorbidities based on the different number and types of comorbidities, and the relationship between the lymphocyte counts and subsets with the number and types of comorbidities was investigated.ResultsCompared with the control group, the lymphocyte counts and T cell subsets were significantly increased in the groups with comorbidities, but both B and NK cell subsets were significantly decreased in the no comorbidity group and in most of the groups with comorbidities (all P<0.05). In the three comorbidities group, the lymphocyte counts and T cell subsets were all significantly decreased, but the CD56+ percentage was obviously increased (all P<0.05). The number of comorbidities was negatively correlated with the lymphocyte counts and the T and NK cell subsets. A negative correlation also existed between cancer and both the lymphocyte counts and the T cell subsets, between chronic hepatitis B and the lymphocyte counts, and between chronic kidney disease and the CD3+ counts. A positive correlation existed between nonalcoholic fatty liver disease (NAFLD) disease and both lymphocyte and CD3+ counts. The risk factors were number of comorbidities for the lymphocyte count, CD3+CD4+ and CD3+CD8+ percentages, NAFLD for the lymphocyte and CD3+ counts, cardiovascular diseases for CD3+CD4+ and CD3+CD8+ percentages, diabetes mellitus for the CD3+CD8+ percentage, and cancer for the CD3+ percentage, respectively.Conclusions High numbers of comorbidities and specific comorbidities could impact the immune response of COVID-19 patients. This study provides a reference for clinicians in the identification of suitable and timely immunotherapy for COVID-19 patients.Clinical Trial Registryhttps://www.chictr.org.cn/enindex.aspx, identifier ChiCTR2000034563.
... It has been discovered that nCOVID-19 is spread from animal to human; several afflicted people claimed to have contracted the virus after visiting a local fish and wild animal market in Wuhan on 28 November [2]. Following that, other researchers confirmed that transmission can also occur from one person to another [3]. According to World Health Organization data, the number of reported laboratory-confirmed human infections in 187 countries, territories, or places around the world reached 292,142 on 21 March 2020, with 12,784 mortality cases [4]. ...
... Description of the model's parameters(3). ...
Article
Full-text available
A novel coronavirus infection system is established for the analytical and computational aspects of this study, using a fuzzy fractional evolution equation (FFEE) stated in Caputo’s sense for order (1,2). It is constructed using the FFEE formulated in Caputo’s meaning. The model consist of six components illustrating the coronavirus outbreak, involving the susceptible people K‘(w), the exposed population L‘(w), total infected strength C‘(w), asymptotically infected population M‘(w), total number of humans recovered E‘(w), and reservoir Q‘(w). Numerical results using the fuzzy Laplace approach in combination with the Adomian decomposition transform are developed to better understand the dynamical structures of the physical behavior of COVID-19. For the controlling model, such behavior on the generic characteristics of RNA in COVID-19 is also examined. The findings show that the proposed technique of addressing the uncertainty issue in a pandemic situation is effective.
... It has been reported that COVID-19 has the largest non-fragment genome among all RNA virus species, with a length of about 30 kb . Because of this, the plasticity of the genome is enhanced, which increases the possibility of recombination and mutation of the genome, and improves its chances of cross-species transmission and genetic diversity (Ji, et al., 2020). ...
Article
Full-text available
Network pharmacology was rapidly developed based on multidisciplinary holistic analysis of biological systems, which has become a popular tool in traditional Chinese medicine (TCM) research in recent years. Its characteristics of integrity and systematization provide a new approach for the study on complex TCM systems, which has many similarities with the holistic concept of TCM. It has been widely used to explain the mechanism of TCM treatment of diseases, drug repositioning, and interpretation of compatibility of TCM prescriptions, to promote the modernization of TCM. The use of TCM have provided crucial support on prevention and treatment of diseases such as the famous “three medicines and three prescriptions”. Furthermore, TCM has become an important part of the treatment of COVID-19 and is one of the main contents of the “Chinese plan” to fight the epidemic. The current review demonstrated the role of TCM in treating diseases with multiple components, multiple targets, and multiple pathways, interprets the connotation of TCM treatment method selection based on pathogenesis and also discusses the application of network pharmacology in the study of COVID-19 treatment in TCM including single drug and prescription. However, there are still some shortcomings such as the lack of experimental verification and regular upgrading of the TCM pharmacology network. Therefore, we must pay attention to the characteristics of TCM and develop a network pharmacology method suitable for TCM system research when applying network pharmacology to TCM research.
... Based at large variety of infected human beings, has been exposed to wet animal market in the Wuhan City wherein live animals are offered too, so there is a probability that is may be a origin Initial scientist has found out two species of the snakes that may be a responsible reservoir of COVID-19. Although till now, there is no strong evidence that corona virus resides except birds and mammals [35,36]. After analysis of genomic sequences and comparison it was found that there is 88% similarity among COVID-19 and two bat-originated severe acute respiratory syndrome (SARS)-like corona viruses [37,38], It indicates that mammals are hyperlink between COVID-19 and human beings. ...
Article
Full-text available
Article is about extension of covid 19 these days
... Bats (Chiroptera spp.) are likely to be the storage hosts of COVID-19 [2]. Sunda pangolin (Manis javanica) and other wild animals may be intermediate hosts in the process of virus transmission and mutation [3][4][5][6]. The prevention of zoonotic diseases has received unprecedented attention. ...
Article
Full-text available
Since the beginning of 2020, China has banned the consumption of wild animals to combat the spread of zoonoses. Most existing studies focus on the intention and behavior of wildlife consumption and their causes; however, few have looked at public willingness to resist wildlife consumption, as well as the cause and effects of such actions. In this study, a framework for an extended theory of planned behavior was constructed. Based on a 7-point Likert scale, a sample of 1194 respondents from eight provinces across China was obtained through an online survey. Structural equation modeling was used to analyze netizen behavioral intention to resist consuming wild animals and their causes to provide a reference for the implementation and optimization of relevant policies. The study model passed the goodness-of-fit test, confirming the robustness of the results. The results showed that Chinese netizens’ intention to resist consuming wild animals was moderate, with 55.19% willing to participate in activities against it, i.e., it is important to resist eating wild animals as a standard. Attitude, subjective norm, perceived behavioral control, and past experience of the Chinese netizen had significant positive effects on resistance intention, i.e., (1) netizens’ current living area with severe outbreaks were more likely to resist wildlife consumption, (2) highly knowledge level netizens were more likely to resist wildlife consumption than less knowledgeable ones, and (3) lower income level had higher behavioral intentions of netizens. The findings suggest that the government must take a lead role in wildlife protection and strengthen its restrictions, laws, and regulations. The media should also be used to promote conservation and popularize a protective message in favor of wild animals. Public quality and assurance of wildlife protection should be culturally reinforced to effectively ban the illegal trade of wild animals and their products.
... Vaccines targeting the S protein neutralize viral infections due to their ability to produce antibodies that may block membrane fusion and virus binding. In the case of SARS-CoV-2, the S protein is largely involved in membrane fusion and receptor binding [94]; hence, the main targets for subunit vaccines are coronavirus structural proteins such as the S protein, which is the major antigenic determinant, as it elicits NAbs and host defense mechanisms [95]. ...
Article
The coronavirus disease 2019 (COVID-19) pandemic rapidly spread globally. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is a positive-sense single-stranded RNA virus with a reported fatality rate ranging from 1% to 7%, and people with immune-compromised conditions, children, and older adults are particularly vulnerable. Respiratory failure and cytokine storm-induced multiple organ failure are the major causes of death. This article highlights the innate and adaptive immune mechanisms of host cells activated in response to SARS-CoV-2 infection and possible therapeutic approaches against COVID-19. Some potential drugs proven to be effective for other viral diseases are under clinical trials now for use against COVID-19. Examples include inhibitors of RNA-dependent RNA polymerase (remdesivir, favipiravir, ribavirin), viral protein synthesis (ivermectin, lopinavir/ritonavir), and fusion of the viral membrane with host cells (chloroquine, hydroxychloroquine, nitazoxanide, and umifenovir). This article also presents the intellectual groundwork for the ongoing development of vaccines in preclinical and clinical trials, explaining potential candidates (live attenuated-whole virus vaccines, inactivated vaccines, subunit vaccines, DNA-based vaccines, protein-based vaccines, nanoparticle-based vaccines, virus-like particles and mRNA-based vaccines). Designing and developing an effective vaccine (both prophylactic and therapeutic) would be a long-term solution and the most effective way to eliminate the COVID-19 pandemic.
... Results from studies to date indicate that 2019-nCoV has the most similar sequence with bat coronavirus ). More interestingly, there is homologous recombination within the S glycoprotein of 2019-nCoV, which may explain its interspecies transmission and limited spread from human to human (Ji et al. 2020). The amino-terminal domain of the S protein is significantly unique for different host receptors, though that cross-transmission happens because of RNA recombination, which can alter the tissue tropism and virus virulence (Holmes 2005). ...
Article
Of all known airborne diseases in the twenty-first century, coronavirus disease 19 (COVID-19) has the highest infection and death rate. Over the past few decades, animal origin viral diseases, notably those of bats-linked, have increased many folds in humans with cross-species transmissions noted and the ongoing COVID-19 pandemic has emphasized the importance of understanding the evolution of natural hosts in response to viral pathogens. Cross-species transmissions are possible due to the possession of the angiotensin-converting enzyme 2 (ACE2) receptor in animals. ACE2 recognition by SARS-CoV-2 is a critical determinant of the host range, interspecies transmission, and viral pathogenesis. Thus, the phenomenon of breaking the cross-species barrier is mainly associated with mutations in the receptor-binding domain (RBD) of the spike (S) protein that interacts with ACE2. In this review, we raise the issue of cross-species transmission based on sequence alignment of S protein. Based on previous reports and our observations, we can conclude that the occurrence of one of two mutations D614G or Y453F is sufficient for infection of minks by SARS-CoV-2 from humans. Unfortunately, D614G is observed in the world’s most common line of virus B.1.1.7 and the latest SARS-CoV-2 variants B.1.617.1, B.1.617.2, and B.1.617.3 too.
... The coronavirus disease 2019 (COVID- 19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first case of this viral pneumonia of unknown aetiology was reported on December 12, 2019, in Wuhan, China [1]. SARS-CoV-2 can be transmitted through contact and droplets, which spread during coughing or sneezing [2]. ...
Article
Full-text available
Background Patients with comorbidities have an increased risk for severe coronavirus disease (COVID-19) symptoms, including abnormal inflammation. Chest X-rays and C-reactive protein (CRP) level are frequently used to evaluate the severity of inflammation. The aim of this study was to investigate the correlation between comorbidities, chest X-ray findings, and CRP level in patients with COVID-19. Materials and methods This was a cross-sectional, analytic, observational study performed using a quantitative approach. The study population included in patients with confirmed COVID-19. Secondary data from the medical records of the patients were analysed to determine the correlations between comorbidities, chest X-rays, and CRP level. Results The data of 167 patients (87 [52.1%] females and 80 [47.9%] males) were evaluated. Regarding comorbidities, 86 (51.5%) patients had hypertension, 66 (39.5%) had diabetes mellitus, and 17 (10.2%) had dyspepsia. Chest X-rays showed that 144 (86.2%) patients had pneumonia, whereas 23 (13.8%) did not. A total of 143 (85.6%) patients showed increased CRP levels, whereas 24 (14.4%) did not show any increase. Patients who showed pneumonia on chest X-rays tended to have increased CRP levels. The results also showed that chest X-ray findings were correlated with CRP level. Diabetes mellitus and hypertension were significantly correlated with CRP level (p = 0.05), whereas dyspepsia did not show a significant relationship with CRP level (p > 0.05). Patients with hypertension had a 2.709-fold risk of having increased CRP level compared with patients without hypertension. Patients with pneumonia had a 2.953-fold increased risk for increased CRP level compared to those without pneumonia. Conclusion Hypertension and diabetes mellitus are significantly correlated with CRP level. Chest X-ray finding is also significantly correlated with CRP level.
... Initial investigation reports identified two species of snakes that could act as a reservoir for the virus. However, there was insufficient evidence to prove the fact (Ji et al. 2020). ...
Chapter
Despite the recent announcement of the new pathogenic coronavirus to man, SARS-CoV2, a large number of publications are presented to the scientific community. An organized and systematic review of the epidemiological, etiological, and pathogenic factors of COVID-19 is presented. This is a systematic review using the databases MEDLINE, EMBASE, Web of Science, SCIELO; the descriptors coronavirus, SARS-CoV-2, etiology, epidemiology, pathophysiology, pathogenesis, COVID-19, with publications from December 2019 to January 2021, resulting in more than 800 publications and 210 selected. The data suggest that COVID-19 is associated with SAR-CoV-2 infection, with the transmission of contagion by fomites, salivary droplets, and other forms, such as vertical and fecal–oral. The bat and other vertebrates appear to be reservoirs and part of the transmission chain. The virus uses cell receptors to infect human cells, especially ACE2, like other coronaviruses. Heat shock proteins have different roles in the infection, sometimes facilitating it, sometimes participating in more severe conditions, when not serving as a therapeutic target. The available data allow us to conclude that COVID-19 is a pandemic viral disease, behaving as a challenge for public health worldwide, determining aggressive conditions with a high mortality rate in patients with risk factors, without treatment, but with the recent availability of the first vaccines.
... There is a alteration of five nucleotides between SARS and SARS-CoV-2 [68]. The variations at the level of spikes on receptor binding ligands [23,33,55,85] is accountable for zoonotic spillover and crossing of the species barrier [2,22,24,40,51,52,56,58,68,69,76,85,92,100]. The microscopic images of the structure of the SARS-CoV-2 approves the transformation in spike glycoprotein of SARS-CoV-2 [68]. ...
Article
Full-text available
Coronavirus Disease 2019 (COVID-19) is an evolving communicable disease caused due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which has led to a global pandemic since December 2019. The virus has its origin from bat and is suspected to have transmitted to humans through zoonotic links. The disease shows dynamic symptoms, nature and reaction to the human body thereby challenging the world of medicine. Moreover, it has tremendous resemblance to viral pneumonia or Community Acquired Pneumonia (CAP). Reverse Transcription Polymerase Chain Reaction (RT-PCR) is performed for detection of COVID-19. Nevertheless, RT-PCR is not completely reliable and sometimes unavailable. Therefore, scientists and researchers have suggested analysis and examination of Computing Tomography (CT) scans and Chest X-Ray (CXR) images to identify the features of COVID-19 in patients having clinical manifestation of the disease, using expert systems deploying learning algorithms such as Machine Learning (ML) and Deep Learning (DL). The paper identifies and reviews various chest image features using the aforementioned imaging modalities for reliable and faster detection of COVID-19 than laboratory processes. The paper also reviews and compares the different aspects of ML and DL using chest images, for detection of COVID-19.
... Since the end of 2019 to now, public health issues have been exacerbated primarily by the consequences of the sudden spread of a new infectious disease. Many names have been used to identify the new virus and however now the name covid-19 reflects the new virus as suggested by WHO [2]. While the Chinese health authorities took strict measures, the new infection spread rapidly in Wuhan on 30-Dec-2019 [1]. ...
Article
Almost existing anti-viral drugs are only organic molecules that are able to circumvent the system the virus works with, which leaves it facing the immune system of our bodies and then kills it. Unfortunately, this type of pharmacological fight did not succeed in a way to overcome this virus, so it became necessary to think outside the box, to find a drug that would kill the virus or alter its protein structure. This research aims to prepare silver nanoparticle (AgNPs) by the green method depending on the reaction of the silver nitrate (safe for humans) with the phoenix dactylifera extract (safe for humans) and then coated with the hydroxychloroquine (HQ, known antiviral drug). This substance will fight the virus with different mechanisms (i) silver will carry the drug to cells easily, and then (ii) nano silver will perform a physical inhibition of the virus and thus reduce its susceptibility to binding to host cells. In addition, (iii) silver nanoparticle is much smaller than the size of the virus which qualifies it to cross into the virus and change the structure of RNA. Furthermore, (iv) it is possible for silver to interact with the amino and carboxylic ends in the virus proteins. The results of TCID50 shows that the prepared nano drug is able to reduce the viability of covid-19 to about 22% using 400 mg/ml of AgNPs/HQ. The resulted nanodrug was also used for healing the wound infected with S. aureus and the histological results revealed that all of the disease symptoms improved, with the epidermal layer multiplying quickly and the infected wounds healing quickly.
... The genome of SARS-CoV-2 is 96% identical to that of the RaTG13 coronavirus isolated from bat droppings, which supports a hypothesis that bats are the most likely primary host of SARS-CoV-2 [13,14]. However, various assumptions have been also made about potential intermediate host of this virus including snakes [15], lizards [16], minks [8] and pangolins [17,18], but an intermediate host has not been found yet, and there may be several hosts [19]. Meanwhile, the identification of the natural carrier of the virus is very important to control its spread. ...
Article
Full-text available
The SARS-CoV-2 is the third coronavirus in addition to SARS-CoV and MERS-CoV that causes severe respiratory syndrome in humans. All of them likely crossed the interspecific barrier between animals and humans and are of zoonotic origin, respectively. The origin and evolution of viruses and their phylogenetic relationships are of great importance for study of their pathogenicity and development of antiviral drugs and vaccines. The main objective of the presented study was to compare two methods for identifying relationships between coronavirus genomes: phylogenetic one based on the whole genome alignment followed by molecular phylogenetic tree inference and alignment-free clustering of triplet frequencies, respectively, using 69 coronavirus genomes selected from two public databases. Both approaches resulted in well-resolved robust classifications. In general, the clusters identified by the first approach were in good agreement with the classes identified by the second using K -means and the elastic map method, but not always, which still needs to be explained. Both approaches demonstrated also a significant divergence of genomes on a taxonomic level, but there was less correspondence between genomes regarding the types of diseases they caused, which may be due to the individual characteristics of the host. This research showed that alignment-free methods are efficient in combination with alignment-based methods. They have a significant advantage in computational complexity and provide valuable additional alternative information on the genomes relationships.
... Beyond its medical importance, B. multicinctus carries economic value in Asia, where it is often traded for consumption (Wong et al., 2009;Ji et al., 2020), and is known to have been heavily exported from mainland China (Zhou and Jiang, 2005). Distinguishing B. wanghaotingi and B. multicinctus in Hong Kong, as well as in mainland China, would be crucial for adequately monitoring the trade and conservation statuses of these two species. ...
... Snakes had once been considered as the original source, or an intermediate host, of SARS-CoV-2, but this was proven not to be the case [97]. Studies aligning the key residues of the hACE2 utilized in binding with the SARS-CoV-2 S-protein have demonstrated that snakes share less than 56% similarity in their ACE2 sequences [98]. ...
Article
Full-text available
The emergence of multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the importance of possible animal-to-human (zoonotic) and human-toanimal (zooanthroponotic) transmission and potential spread within animal species. A range of animal species have been verified for SARS-CoV-2 susceptibility, either in vitro or in vivo. However, the molecular bases of such a broad host spectrum for the SARS-CoV-2 remains elusive. Here, we structurally and genetically analysed the interaction between the spike protein, with a particular focus on receptor binding domains (RBDs), of SARS-CoV-2 and its receptor angiotensin-converting enzyme 2 (ACE2) for all conceivably susceptible groups of animals to gauge the structural bases of the SARS-CoV-2 host spectrum. We describe our findings in the context of existing animal infection-based models to provide a foundation on the possible virus persistence in animals and their implications in the future eradication of COVID-19.
... Due to the SARS-CoV-2 RNA content and its high potential for emergence, respiratory infections caused by the virus have recently led to deadly endemics in humans, such as SARS and measles. The causative agent of these two types of coronavirus diseases is zoonotic and belongs to the genus β-coronavirus of the coronaviridae family [9][10][11]. The first case of Middle East respiratory syndrome (MERS) was observed in Saudi Arabia in 2011-2012, of which 2495 cases have been reported since then, of which 858 cases were associated with death and the death rate was estimated at 34.4%. ...
Article
Full-text available
A new epidemic of acute respiratory viral pneumonia was discovered in central China at the end of 2019. The disease was given the name coronavirus disease 2019 (COVID-19), and the virus that caused this disease was known as severe acute respiratory syndrome coronavirus (SARS-CoV-2). So far, diagnostic methods have been focused on (a) human antibody detection, (b) viral antigen detection and (c) viral gene detection, the latter using RT-PCR being the most accurate approach. In this paper, we present a summary of the COVID-19 pandemic, clinical features and epidemiology and pathogenesis. Also, we focus on the recent advances in bioanalytical diagnostic methods based on various techniques for SARS-CoV-2 sensing that have recently been published (2020–2021). Furthermore, we present the mechanisms, advantages and disadvantages of the most common biosensors for COVID-19 detection, which include optical, electrochemical and piezoelectric biosensors as well as wearable and smart nanobiosensors, immunosensors, aptasensors and genosensors.
... On January 7, the China CDC succeeded in isolating the first novel coronavirus strain; the next day, an expert evaluation team designated by the NHC initially identified a new coronavirus as the cause of the disease; on January 15, the NHC unveiled the first version of the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia and Protocol on Prevention and Control of Novel Coronavirus Pneumonia. On January 20, after three weeks of continuous investigation of the outbreak, the third working group confirmed that the disease could be spread between humans after finding two cases in southern Guangdong province among people who had not been to Wuhan (Ji et al. 2020). ...
... The review [8] aims to analyze the genetic similarity and diversity of coronavirus strains, which could reveal SARS-sensitive CoV2 s antigenic targets. According to the research results [9], the 2019-nCoV appears to be a hybrid virus between the bat coronavirus and an undiscovered coronavirus. In terms of virulence, the immunological response of the body, and vaccine efficiency, each strain is different [10]. ...
Article
Full-text available
Coronaviruses are viruses that infect the respiratory system of humans. Besides high mortality rates among the population, they brought about several economic crises on a global scale. Methods. To study and identify features in the genetic composition of the nucleotide sequences of various coronaviruses, we applied copyright algorithms and visualization, which allowed us to compare the biochemical parameters of diverse RNA coronaviruses in a visual form. Results. The article provides examples of different approaches to imaging coronaviruses. We have provided examples of coronavirus RNA structure visualization in various parametric spaces (1-D and 2-D). We employed various visualization types, including structural, integral, and frequency. The research discussed methods of visualization. Our team developed visualization and comparative analysis of coronavirus serotypes and visualization of SARS-CoV-2 coronavirus datasets. Discussion followed on the visualization results. The presented techniques and the results allowed for displaying the structure of RNA sequences of coronaviruses in spaces of various dimensions. Conclusions. According to our findings, the proposed method contributes to the visualization of the genetic coding of coronaviruses. We discussed the issues of machine learning and neural network technology concerning the analysis of coronaviruses based on the presented approach. The described line of research is essential for the study and control of complex quantum mechanical systems, such as RNA or DNA.
... When zoonotic animal viruses spread in humans, they can become a serious health threat because the population is immunologically naïve [10,11], leading to global pandemics such as COVID-19 currently. SARS-CoV-2 has shown particularly high transmissibility compared to previous respiratory CoVs, [12] thus any research should be conducted in a BSL-3 environment [13]. ...
Article
Full-text available
Effective airborne transmission of coronaviruses via liquid microdroplets requires a virion structure that must withstand harsh environmental conditions. Due to the demanding biosafety requirements for the study of human respiratory viruses, it is important to develop surrogate models to facilitate their investigation. Here we explore the mechanical properties and nanostructure of transmissible gastroenteritis virus (TGEV) virions in liquid milieu and their response to different chemical agents commonly used as biocides. Our data provide two-fold results on virus stability: First, while particles with larger size and lower packing fraction kept their morphology intact after successive mechanical aggressions, smaller viruses with higher packing fraction showed conspicuous evidence of structural damage and content release. Second, monitoring the structure of single TGEV particles in the presence of detergent and alcohol in real time revealed the stages of gradual degradation of the virus structure in situ. These data suggest that detergent is three orders of magnitude more efficient than alcohol in destabilizing TGEV virus particles, paving the way for optimizing hygienic protocols for viruses with similar structure, such as SARS-CoV-2.
... Let's observe the models related to the respiratory and blood circulatory systems because of several reasons. First, according to the current information, exactly these systems are the most affected by the SARS-CoV-2 virus [14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Secondly, in the theory of adaptation developed by Meyerson, exactly these systems responded most noticeably to changes of living conditions [28,29]. ...
Article
The aim of the work was to create a complex mathematical model simulating the course of the disease caused by the SARS-CoV-2 virus on the level of interaction between functional systems of organism and pharmacological correction of organism hypoxic states arising in the complicated course of the disease. In the present work the methods of mathematical modeling and theory of optimal control of moving objects were used. The proposed integrated mathematical model consisted on the mathematical models of functional systems of respiration and blood circulation, thermoregulation, immune response, erythropoesis, and pharmacological correction. Individual patient data were taken for this model, and the disturbing effect in the form of viral disease was simulated. The reactions of functional respiratory and blood circulatory systems were predicted. Partial pressures of respiratory gases in alveolar spaces and their tensions in lung capillaries blood, arterial and mixed venous blood, and tissue fluid were calculated. Further the intravenous injection of antihypoxant was simulated and the values of the same parameters were calculated. In such a way it was possible to choose the most optimal way of hypoxic state correction for any individual. This model is theoretical only for today because the models of respiratory and blood circulation systems were designed for the average person and it does not suppose peculiarities of individual persons infected with SARS-CoV-2. In particular, this concerns the pequliarities of gas exchange in the alveolar space and characteristics of respiratory gases diffusion through the alveolar-capillary and capillary-tissue membranes. However, it is one of possible directions for solving the complex tasks related to treatment of the disease caused by SARS-CoV-2 virus. In the result of the work the complex of information support for the imitation of viral disease course was developed at the level of interaction of organism functional systems, as well as pharmacological correction of caused by it hypoxic states
... In late 2019, a novel coronavirus (CoV) strain associated with fatal respiratory illness was reported [7]. The World Health Organization named this virus as the 2019 novel CoV (2019-nCoV) [8]. On January 10, 2020, the first complete genome sequence of the novel CoV was reported, which helped researchers for rapid detection of the virus in patients by using reverse-transcription polymerase chain reaction (RT-PCR) methods [9,10]. ...
... Let's observe the models related to the respiratory and blood circulatory systems because of several reasons. First, according to the current information, exactly these systems are the most affected by the SARS-CoV-2 virus [14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Secondly, in the theory of adaptation developed by Meyerson, exactly these systems responded most noticeably to changes of living conditions [28,29]. ...
Article
The aim of the work was to create a complex mathematical model simulating the course of the disease caused by the SARS-CoV-2 virus on the level of interaction between functional systems of organism and pharmacological correction of organism hypoxic states arising in the complicated course of the disease. In the present work the methods of mathematical modeling and theory of optimal control of moving objects were used. The proposed integrated mathematical model consisted on the mathematical models of functional systems of respiration and blood circulation, thermoregulation, immune response, erythropoesis, and pharmacological correction. Individual patient data were taken for this model, and the disturbing effect in the form of viral disease was simulated. The reactions of functional respiratory and blood circulatory systems were predicted. Partial pressures of respiratory gases in alveolar spaces and their tensions in lung capillaries blood, arterial and mixed venous blood, and tissue fluid were calculated. Further the intravenous injection of antihypoxant was simulated and the values of the same parameters were calculated. In such a way it was possible to choose the most optimal way of hypoxic state correction for any individual. This model is theoretical only for today because the models of respiratory and blood circulation systems were designed for the average person and it does not suppose peculiarities of individual persons infected with SARS-CoV-2. In particular, this concerns the pequliarities of gas exchange in the alveolar space and characteristics of respiratory gases diffusion through the alveolar-capillary and capillary-tissue membranes. However, it is one of possible directions for solving the complex tasks related to treatment of the disease caused by SARS-CoV-2 virus. In the result of the work the complex of information support for the imitation of viral disease course was developed at the level of interaction of organism functional systems, as well as pharmacological correction of caused by it hypoxic states
... The origin of this virus is claimed to be from animals especially wild animals as Wuhan is one of the important cities in which people are quite interested in wild animals and animal market is popular in Wuhan. 1 Subsequently, it has been discovered that human to human transmission is also possible. 2 This novel coronavirus is spread through close contact and respiratory droplets while in serious cases causing severe atypical pneumonia. 3 Other complications including sepsis, infection of the heart, liver, the digestive tract and multiple organ failure may arise and are especially dangerous in more susceptible groups such as the elderly and people with underlying comorbidities. ...
Article
Full-text available
The main purpose of present paper is to investigate the nonlinear model of COVID‐19 (novel coronavirus) computationally. The SITR model is designed according to four classifications of Susceptible (S), Infectious (I), Treatment (T) and Recovered (R). Two convenient and effective numerical techniques namely the Adams–Bashforth Method (ABM) and Milne‐Simpson Method (MSM) are employed to analyze the epidemic model. The influences of the contact rate parameter (β), recovery parameter (μ) and death parameter (α) on the variables including S, I and R are studied comprehensively. The obtained findings indicate that by increasing the contact rate parameter the infectious and recovered categories enhance but the susceptible mechanism decreases.
... Homologous recombination occurs between parental RNA molecules that are similar in sequence, with the recombination region being located on the matching, homologous sequences. The resulting recombinant RNA contains the sequence and structure of the parental RNA molecules (Ji et al., 2020;Alatorre-García et al., 2021;Crook et al., 2021). Similarly, aberrant homologous recombination also requires two parental RNA molecules with similar sequences. ...
Article
Full-text available
RNA recombination is a major driver of genetic shifts tightly linked to the evolution of RNA viruses. Genomic recombination contributes substantially to the emergence of new viral lineages, expansion in host tropism, adaptations to new environments, and virulence and pathogenesis. Here, we review some of the recent progress that has advanced our understanding of recombination in positive-strand RNA viruses, including recombination triggers and the mechanisms behind them. The study of RNA recombination aids in predicting the probability and outcome of viral recombination events, and in the design of viruses with reduced recombination frequency as candidates for the development of live attenuated vaccines. Surveillance of viral recombination should remain a priority in the detection of emergent viral strains, a goal that can only be accomplished by expanding our understanding of how these events are triggered and regulated.
Article
The combination of molecular dynamics simulations and quantitative calculations as a powerful tool for screening molecules.
Article
Full-text available
Conflicto de intereses: Ninguno El estudio no contó con financiamiento. Recibido: 28 de diciembre de 2021 / Aceptado: 21 de febrero de 2022 Resumen Introducción: El umbral de ciclo (en inglés cycle threshold-Ct) de la reacción de polimerasa en cadena en tiempo real con transcripción reversa (RT-qPCR) indica la concentración relativa de una secuencia de ARN; este valor se ha relacionado con la expresión de cuadros clínicos en infecciones virales. Objetivo: Determinar la correlación entre el valor Ct y la clasificación clínica de la COVID-19. Método: Se realizó un estudio transeccional correlacional; los valores Ct se obtuvieron mediante RT-qPCR dirigida al gen N del SARS-CoV-2 agrupándolos mediante un estimador robusto central y relacionándose con la clasifi-cación clínica de la COVID-19. Resultados: De los 718 casos incluidos en el estudio; 77,7% (558) fueron leves; 21,3% (153) moderados y 1% (7) graves. El valor Ct se agrupó en niveles: Ct bajo ≤ 18,83; Ct medio > 18,83-30,10 y Ct alto > 30,10. Existió correlación significativa inversa débil (p = 0,002; rho de Spearman =-0,117) entre el valor Ct y la clasificación clínica. Las características: sexo, edad menor a 65 años, fiebre, escalofrío, diarrea, anosmia y sobrepeso-obesidad estuvieron asociadas al valor de Ct. Conclusión: A menor valor Ct se espera una clasificación de mayor gravedad de la COVID-19; no obstante, debido a que la correlación es débil, su utilidad como pre-dictor de gravedad es limitada. Palabras clave: infecciones por coronavirus; reacción de polime-rasa en cadena; carga viral; ciclo umbral. Abstract Background: The cycle threshold (Ct) of real-time reverse transcription PCR (RT-qPCR) indicates the relative concentration of an RNA sequence, this value has been related to clinical profile in viral infections. Aim: To determine the correlation between the Ct value and the clinical classification of COVID-19. Method: A correlational cross-sectional study was carried out, the Ct values were obtained by RT-qPCR directed to the N gene of SARS-CoV-2, grouping them by means of a central robust estimator and related to the clinical classification of COVID-19. Results: Of the 718 cases included in the study; 77.7% (558) were mild; 21.3% (153) moderate and 1% (7) severe. The Ct value was grouped into levels: low Ct ≤ 18.83; medium Ct> 18.83-30.10 and high Ct> 30.10. There was a weak inverse significant correlation (p = 0.002; Spearman's rho =-0.117) between the Ct value and the clinical classification. The characteristics: sex, age under 65 years, fever, chills, diarrhea, anosmia, and overweight-obesity were associated with the Ct value. Conclusion: The lower the Ct value, a classification of greater severity of COVID-19 is expected, however, because the correlation is weak, its usefulness as a severity predictor is limited.
Chapter
Since the outbreak of the novel SARS-CoV-2, i.e., in December 2019, in Wuhan, China, more than 110 million cases have been reported, with 2.5 million deaths worldwide. It is not the first time, earlier in 2002–2003 SARS-CoV and in 2010 MERS-CoV outbreaks were reported. However, in 2019 novel SARS-CoV-2 outbreak prevailed to a great extent worldwide. Still, we are in the middle of a pandemic and seek effective vaccines and therapeutics for prevention and complete cure, respectively. There are new strains of novel SARS-CoV2 reported in a different part of the world. Considering the research data and statistics from CDC and WHO, the novel SARS-CoV-2 is the second most deadly viral outbreak after the Spanish Flu in 1918. Compared to previous coronavirus outbreak cases, the novel SARS-CoV-2 attack was reported to be more transmissible but less fatal. Among the top five countries worst affected by novel SARS-CoV-2 infection and mortality are the United States, India, Brazil, Russia, and the United Kingdom. Similarly, many countries in Europe, including Spain and Italy have endured a similar impact with viral outbreaks. The pandemic started in China and traveled to Europe, the United States and the American continent, and many Asian countries, including Russia and India, which are “hot spots” for virus infection and disease outbreak. In the first wave of the virus outbreak, many countries including China, South Korea, Japan, New Zealand, etc., successfully controlled and contained the virus, using strict social distancing and other containment measures. The reproductive number (R0) and fatality rate of COVID-19 disease caused by novel SARS-CoV-2 infection vary among different populations. However, infection and disease are a function of several risk factors, including age, sex, comorbidity, and strain of novel SARS-CoV-2. Simultaneously, there is a massive effort in research for diagnostic, therapeutic, and vaccine development. It was the first time in human history where a clinical diagnosis was implemented very early in the case of a pandemic. Several antiviral drugs, antiinflammatory agents, immune modulators, and vitamins were used to control the COVID-19 disease.
Article
Full-text available
Over the last 20 years, both severe acute respiratory syndrome coronavirus-1 and severe acute respiratory syndrome coronavirus-2 have transmitted from animal hosts to humans causing zoonotic outbreaks of severe disease. Both viruses originate from a group of betacoronaviruses known as subgroup 2b. The emergence of two dangerous human pathogens from this group along with previous studies illustrating the potential of other subgroup 2b members to transmit to humans has underscored the need for antiviral development against them. Coronaviruses modify the host innate immune response in part through the reversal of ubiquitination and ISGylation with their papain-like protease (PLpro). To identify unique or overarching subgroup 2b structural features or enzymatic biases, the PLpro from a subgroup 2b bat coronavirus, BtSCoV-Rf1.2004, was biochemically and structurally evaluated. This evaluation revealed that PLpros from subgroup 2b coronaviruses have narrow substrate specificity for K48 polyubiquitin and ISG15 originating from certain species. The PLpro of BtSCoV-Rf1.2004 was used as a tool alongside PLpro of CoV-1 and CoV-2 to design 30 novel noncovalent drug-like pan subgroup 2b PLpro inhibitors that included determining the effects of using previously unexplored core linkers within these compounds. Two crystal structures of BtSCoV-Rf1.2004 PLpro bound to these inhibitors aided in compound design as well as shared structural features among subgroup 2b proteases. Screening of these three subgroup 2b PLpros against this novel set of inhibitors along with cytotoxicity studies provide new directions for pan-coronavirus subgroup 2b antiviral development of PLpro inhibitors.
Article
In China, Wuhan City became the epicentre of unexplained cases of pneumonia in December 2019 and was temporarily labelled as, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). World Health Organization renamed it to coronavirus disease 2019 (COVID-19) in February 2020. In COVID-19 patients hematological profile showed increased total leukocyte count (TLC) and neutrophilic count, while decrease in other hematological parameters. The mild increase in TLC was found in severe disease patients; however significant increase was associated with clinical worsening and poor outcome. Significant elevation of various biochemical and inflammatory markers was noticed among COVID-19 patients We conducted a retrospective study on RT-PCR confirmed 239 COVID-19 patients who were hospitalized in various COVID-19 facilities from Sept 2020 to Dec 2020. The laboratory data is used in de-identified form and doesn’t reveal identity of any subjects. A total of 239 cases were examined, out of which 176(73.7%) were male and 63(26.3%) were female (M:F ratio= 2.79:1). We found that 104 cases had Hb level ≥ 12gm/dl. We found that maximum patients (175) had TLC level >11000/cumm, 187 patients had ANC level > 7000/cumm. We found that 160 cases had serum urea of >43mg/dl, 134 case with serum creatinine of >1.4gm/dl.134 cases had ALT level of >40IU/L and 143 cases had AST levels of >42IU/L In this study out of 239 cases 126 cases were found to have increased level of all inflammatory markers levels. We found a significant association of various inflammatory markers with haematological and biochemical parameters in COVID-19 patients.
Article
In the early stages of response to the SARS-CoV-2 pandemic, it was imperative for researchers to rapidly determine what animal species may be susceptible to the virus, under low knowledge and high uncertainty conditions. In this scoping review, the animal species being evaluated for SARS-CoV-2 susceptibility, the methods used to evaluate susceptibility, and comparing the evaluations between different studies were conducted. Using the PRISMA-ScR methodology, publications and reports from peer-reviewed and gray literature sources were collected from databases, Google Scholar, the World Organization for Animal Health (OIE), snowballing, and recommendations from experts. Inclusion and relevance criteria were applied, and information was subsequently extracted, categorized, summarized, and analyzed. Ninety seven sources (publications and reports) were identified which investigated 649 animal species from eight different classes: Mammalia, Aves, Actinopterygii, Reptilia, Amphibia, Insecta, Chondrichthyes, and Coelacanthimorpha. Sources used four different methods to evaluate susceptibility, in silico, in vitro, in vivo, and epidemiological analysis. Along with the different methods, how each source described “susceptibility” and evaluated the susceptibility of different animal species to SARS-CoV-2 varied, with conflicting susceptibility evaluations evident between different sources. Early in the pandemic, in silico methods were used the most to predict animal species susceptibility to SARS-CoV-2 and helped guide more costly and intensive studies using in vivo or epidemiological analyses. However, the limitations of all methods must be recognized, and evaluations made by in silico and in vitro should be re-evaluated when more information becomes available, such as demonstrated susceptibility through in vivo and epidemiological analysis.
Article
Full-text available
Given the great utility that having fast, efficient and cost-effective methods for the detection of SARS-CoV-2 in wastewater can have in controlling the pandemic caused by this virus, the development of new dependable and specific SARS-CoV-2 coronavirus sensing devices to be applied to wastewater is essential to promote public health interventions. Therefore, herein we propose a new method to detect SARS-CoV-2 in wastewater based on a carbon nanodots-amplified electrochemiluminescence immunosensor for the determination of the SARS-CoV-2 Spike S1 protein. For the construction of the immunosensor, N-rich carbon nanodots have been synthetized with a double function: to contribute as amplifiers of the electrochemiluminescent signal in presence of [Ru(bpy)3]²⁺ and as antibody supports by providing functional groups capable of covalently interacting with the SARS-CoV-2 Spike S1 antibody. The proposed ECL immunosensor has demonstrated a high specificity in presence of other virus-related proteins and responded linearly to SARS-CoV-2 Spike S1 concentration over a wide range with a limit of detection of 1.2 pg/mL. The immunosensor has an excellent stability and achieved the detection of SARS-CoV-2 Spike S1 in river and urban wastewater, which supplies a feasible and reliable sensing platform for early virus detection and therefore to protect the population. The detection of SARS-CoV-2 Spike S1 in urban wastewater can be used as a tool to measure the circulation of the virus in the population and to detect a possible resurgence of COVID-19.
Article
Full-text available
Our goal was to describe in more detail the evolutionary history of Gamma and two derived lineages (P.1.1 and P.1.2), which are part of the arms race that SARS-CoV-2 wages with its host. A total of 4,977 sequences of the Gamma strain of SARS-CoV-2 from Brazil were analyzed. We detected 194 sites under positive selection in 12 genes/ORFs: Spike, N, M, E, ORF1a, ORF1b, ORF3, ORF6, ORF7a, ORF7b, ORF8, and ORF10. Some diagnostic sites for Gamma lacked a signature of positive selection in our study, but these were not fixed, apparently escaping the action of purifying selection. Our network analyses revealed branches leading to expanding haplotypes with sites under selection only detected when P.1.1 and P.1.2 were considered. The P.1.2 exclusive haplotype H_5 originated from a non-synonymous mutational step (H3509Y) in H_1 of ORF1a. The selected allele, 3509Y, represents an adaptive novelty involving ORF1a of P.1. Finally, we discuss how phenomena such as epistasis and antagonistic pleiotropy could limit the emergence of new alleles (and combinations thereof) in SARS-COV-2 lineages, maintaining infectivity in humans, while providing rapid response capabilities to face the arms race triggered by host immuneresponses.
Chapter
Full-text available
Koronavirüs enfeksiyonu (COVID-19), tüm insanları etkilediği gibi hamile bireyleri de etkilemiştir. Orta derece riskli grupta yer alan gebeler için maternal fetal sağlığın yönetimi konusunda önemli uluslararası kuruluşlar tarafından rehberler yayınlanmaktadır. Bu süreçte maternal fetal sağlık sonuçlarını iyileştirmede anahtar rolün multidisipliner bakım olduğu belirtilmiş olup, sağlık profesyonellerinin önemli sorumluluklar düşmektedir. Bu sorumlulukların başında gebelik ve postpartum dönemde COVID-19 enfeksiyonunun yönetimi ile ilgili güncel literatürü takip etmek ve önerileri uygun şekilde uygulamak vardır.
Article
Several investigations suggested origins of SARS-CoV-2 from the recombination of coronaviruses of various animals, including the bat Rhinolophus affinis and the pangolin Manis javanica, despite the processes describing the adaptation from a reservoir of animals to human are still debated. In this perspective, I will remark two main inconsistencies on the origins of SARS-CoV-2: polypeptide sequence alignment of the S-proteins does not return the expected identity of the receptor-binding motif among most of pangolin-CoVs and SARS-CoV-2; accurate referencing for samplings and sequencing deposition of the ancestral bat coronavirus named RaTG13 was missing since the first reports on the SARS-CoV-2 coronavirus. This contribution aims to stimulate discussion about the origins of SARS-CoV-2 and considers other intermediate hosts as a reservoir for coronavirus.
Article
There was a dramatic spread of three novel coronaviruses (CoVs) – severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 – from the beginning of the twenty-first century. All three infections share similar pathogenesis and clinical presentation, and human-to-human transmission is the most frequent transmission mode for all three CoVs, which spread through respiratory droplets, by direct contact with contaminated surfaces or via inhaling aerosols. Nosocomial transmission plays a major role for SARS-CoV and MERS-CoV but appears to be less critical for SARS-CoV-2. Coronaviruses will very likely continue to be a source of new acute respiratory infections in the future. This is why it is needed to enable a better understanding of the whole spectrum of factors that underlie CoV disease outbreaks. Although a search for specific treatment and vaccine development has to be continued, a strategic preparedness and plan of action should be envisaged in advance. This Review discusses the current knowledge of SARS-CoV, MERS-CoV, SARS-CoV-2 epidemiological determinants and makes particular emphasis on public health interventions that could help in the fight against them.
Article
Full-text available
Many pandemic diseases have emerged in the history and millions of people affected from these diseases. Among the marked pandemics in history, the plague, known as the black death, was recorded to cause the death of 17-54% of the world population. Similar to previous pandemics, as the SARS CoV-2, which emerged in 2019 and belonged to the coronavirus family, caused an epidemic and turned into a pandemic infection, positive cases were detected in more than 483 million people, and more than 6.1 million people died. While this emerging epidemic is still continuing its effects, it has been determined that there are positive cases in pets such as dogs and cats, especially in mink (Neovison vison). Especially in Denmark, Netherlands and Finland, positive animals for COVID-19 were accepted. Unlike the pandemic until today, the COVID-19 has spread to broader geographies and affected many animal species. With the reports that the SARS-CoV-2 - was first transmitted from bats to humans, this viral agent has been accepted as zoonotic, but a complete transmission route has not been shown for its transmission from other animals to humans except bats. It is reported that there is no significant risk of transmission of the virus, which is transmitted primarily by the respiratory route, from both pets and edible foods to humans. Although there are many reports in terrestrial animals, studies on the presence of SARS-CoV-2 - in aquatic animals or aquatic environments and COVID-19 transmission in aquatic animals have doubts. Here we reviewed the viability of the SARS-CoV-2 - in the aquatic environment, transmission to the aquatic ecosystem and aquatic animals, and therefore the risks to humans through water or aquatic products.
Article
Full-text available
Snake soup continues to be an iconic tradition in Cantonese culture. Yet little is known about the relationship between snake soup consumption in Hong Kong, wild snake populations, and the communities depending on this tradition for their livelihoods. We applied an interdisciplinary approach including interviews with shopkeepers and genetic analyses of snake meat samples to determine the species consumed in Hong Kong, their source locations, and shopkeepers’ views on the future of the industry. We genetically identified the common rat snake Ptyas mucosa , widely distributed throughout East and Southeast Asia, and the Javan spitting cobra Naja sputatrix , endemic to Indonesia, as the species most commonly consumed, which was consistent with interview responses. According to interviews, snakes had mostly been imported from mainland China in the past, but now tend to be sourced from Southeast Asia, particularly Indonesia. Interviews also revealed a pessimistic outlook on the continuation of this tradition because of various factors, including a lasting yet misinformed association of snakes with the 2002–2003 outbreak of severe acute respiratory syndrome. Given the COVID-19 pandemic and China's ensuing ban on the consumption of terrestrial wildlife, Hong Kong's snake soup industry will probably continue to rely on Southeast Asian sources to persist. Given the cultural and conservation issues surrounding this tradition, further research on the economic, ecological and social consequences of snake consumption is needed to examine the broader implications of snake soup and similar industries in the region.
Article
Full-text available
The coronavirus-related severe acute respiratory syndrome (SARS-CoV) in 2002/2003, the Middle East respiratory syndrome (MERS-CoV) in 2012/2013, and especially the current 2019/2021 severe acute respiratory syndrome-2 (SARS-CoV-2) negatively affected the national health systems worldwide. Different SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and recently Omicron (B.1.1.529), have emerged resulting from the high rate of genetic recombination and S1-RBD/S2 mutation/deletion in the spike protein that has an impact on the virus activity. Furthermore, genetic variability in certain genes involved in the immune system might impact the level of SARS-CoV-2 recognition and immune response against the virus among different populations. Understanding the molecular mechanism and function of SARS-CoV-2 variants and their different epidemiological outcomes is a key step for effective COVID-19 treatment strategies, including antiviral drug development and vaccine designs, which can immunize people with genetic variabilities against various strains of SARS-CoV-2. In this review, we center our focus on the recent and up-to-date knowledge on SARS-CoV-2 (Alpha to Omicron) origin and evolution, structure, genetic diversity, route of transmission, pathogenesis, new diagnostic, and treatment strategies, as well as the psychological and economic impact of COVID-19 pandemic on individuals and their lives around the world.
Article
Full-text available
Swine coronaviruses (SCoVs) are one of the most devastating pathogens affecting the livelihoods of farmers and swine industry across the world. These include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine respiratory coronavirus (PRCV), porcine hemagglutinating encephalomyelitis virus (PHEV), swine acute diarrhea syndrome coronavirus (SADS-CoV), and porcine delta coronavirus (PDCoV). Coronavirses infect a wide variety of animal species and humans because these are having single stranded-RNA that accounts for high mutation rates and thus could break the species barrier. The gastrointestinal, cardiovascular, and nervous systems are the primary organ systems affected by SCoVs. Infection is usually very common in piglets compared to adult pigs causing high mortality. Bat is implicated to be the origin of all CoVs affecting animals and humans. Since pig is the only domestic animal in which CoVs cause a wide range of diseases; new coronaviruses with high zoonotic potential could likely emerge in the future as observed in the past. The recently emerged severe acute respiratory syndrome coronavirus virus-2 (SARS-CoV-2), causing COVID-19 pandemic in humans, has been implicated to have animal origin, also reported from few animal species, though it’s zoonotic concerns are under investigations. This review discusses SCoVs and their epidemiology, virology, evolution, pathology, wildlife reservoirs, interspecies transmission, spill-over events and highlighting their emerging threats to swine population. The role of pigs amid ongoing SARS-CoV-2 pandemic has also been discussed. A thorough investigation should be conducted to rule out zoonotic potential of SCoVs and to design appropriate strategies for their prevention and control.
Article
Full-text available
Background: The cycle threshold (Ct) of real-time reverse transcription PCR (RT-qPCR) indicates the relative concentration of an RNA sequence, this value has been related to clinical profile in viral infections. Aim: To determine the correlation between the Ct value and the clinical classification of COVID-19. Method: A correlational cross-sectional study was carried out, the Ct values were obtained by RT-qPCR directed to the N gene of SARS-CoV-2, grouping them by means of a central robust estimator and related to the clinical classification of COVID-19. Results: Of the 718 cases included in the study; 77.7% (558) were mild; 21.3% (153) moderate and 1% (7) severe. The Ct value was grouped into levels: low Ct < 18.83; medium Ct> 18.83-30.10 and high Ct> 30.10. There was a weak inverse significant correlation (p = 0.002; Spearman's rho = -0.117) between the Ct value and the clinical classification. The characteristics: sex, age under 65 years, fever, chills, diarrhea, anosmia, and overweightobesity were associated with the Ct value. Conclusion: The lower the Ct value, a classification of greater severity of COVID-19 is expected, however, because the correlation is weak, its usefulness as a severity predictor is limited.
Article
Full-text available
The latest 5G technology is being introduced the Internet of Things (IoT) Era. The study aims to focus the 5G technology and the current healthcare challenges as well as to highlight 5G based solutions that can handle the COVID-19 issues in different arenas. This paper provides a comprehensive review of 5G technology with the integration of other digital technologies (like AI and machine learning, IoT objects, big data analytics, cloud computing, robotic technology, and other digital platforms) in emerging healthcare applications. From the literature, it is clear that the promising aspects of 5G (such as super-high speed, high throughput, low latency) have a prospect in healthcare advancement. Now healthcare is being adopted 5G-based technologies to aid improved health services, more effective medical research, enhanced quality of life, better experiences of medical professionals and patients in anywhere-anytime. This paper emphasizes the evolving roles of 5G technology for handling the epidemiological challenges. The study also discusses various technological challenges and prospective for developing 5G powered healthcare solutions. Further works will incorporate more study on how to expand 5G-based digital society as well as to resolve the issues of safety-security-privacy and availability-accessibility-integrity in future health crises.
Article
Full-text available
Since December 2019, a total of 41 cases of pneumonia of unknown etiology have been confirmed in Wuhan city, Hubei Province, China. Wuhan city is a major transportation hub with a population of more than 11 million people. Most of the patients visited a local fish and wild animal market last month. At a national press conference held today, Dr. Jianguo Xu, an academician of the Chinese Academy of Engineering, who led a scientific team announced that a new‐type coronavirus, tentatively named by World Health Organization as the 2019‐new coronavirus (2019‐nCoV), had caused this outbreak (1).
Article
Full-text available
Zika virus (ZIKV) is a mosquito-borne virus (arbovirus) in the family Flaviviridae, and the symptoms caused by ZIKV infection in humans include rash, fever, arthralgia, myalgia, asthenia and conjunctivitis. Codon usage bias analysis can reveal much about the molecular evolution and host adaption of ZIKV. To gain insight into the evolutionary characteristics of ZIKV, we performed a comprehensive analysis on the codon usage pattern in 46 ZIKV strains by calculating the effective number of codons (ENc), codon adaptation index (CAI), relative synonymous codon usage (RSCU), and other indicators. The results indicate that the codon usage bias of ZIKV is relatively low. Several lines of evidence support the hypothesis that translational selection plays a role in shaping the codon usage pattern of ZIKV. The results from a correspondence analysis (CA) indicate that other factors, such as base composition, aromaticity, and hydrophobicity may also be involved in shaping the codon usage pattern of ZIKV. Additionally, the results from a comparative analysis of RSCU between ZIKV and its hosts suggest that ZIKV tends to evolve codon usage patterns that are comparable to those of its hosts. Moreover, selection pressure from Homo sapiens on the ZIKV RSCU patterns was found to be dominant compared with that from Aedes aegypti and Aedes albopictus. Taken together, both natural translational selection and mutation pressure are important for shaping the codon usage pattern of ZIKV. Our findings contribute to understanding the evolution of ZIKV and its adaption to its hosts.
Article
Full-text available
Coronaviruses have traditionally been associated with mild upper respiratory tract infections throughout the world. In the fall of 2002, a new coronavirus emerged in in Asia causing severe viral pneumonia, i.e., severe acute respiratory syndrome (SARS). Nearly a decade following the SARS epidemic, a new coronavirus causing severe viral pneumonia has emerged, i.e., middle east respiratory syndrome (MERS). Since the initial case of MERS-CoV occurred in June of 2012 in Saudi Arabia there have been 688 confirmed cases and 282 deaths in 20 countries. Although both SARS and MERS are caused by coronaviruses, SARS was characterized by efficient human transmission and relatively low mortality rate. In contrast, MERS is relatively inefficiently transmitted to humans but has a high mortality rate. Given the potential overlap in presentation and manifestation, it is important to understand the clinical and epidemiologic differences between MERS, SARS and influenza.
Article
Full-text available
Phylogenies are increasingly used in all fields of medical and biological research. Moreover, because of the next generation sequencing revolution, datasets used for conducting phylogenetic analyses grow at an unprecedented pace. RAxML (Randomized Axelerated Maximum Likelihood) is a popular program for phylogenetic analyses of large datasets under maximum likelihood. Since the last RAxML paper in 2006, it has been continuously maintained and extended to accommodate the increasingly growing input datasets and to serve the needs of the user community. I present some of the most notable new features and extensions of RAxML, such as, a substantial extension of substitution models and supported data types, the introduction of SSE3, AVX, and AVX2 vector intrinsics, techniques for reducing the memory requirements of the code and a plethora of operations for conducting post-analyses on sets of trees. In addition, an up-to-date, 50 page user manual covering all new RAxML options is available. The code is available under GNU GPL at https://github.com/stamatak/standard-RAxML. Alexandros.Stamatakis@h-its.org.
Article
Full-text available
We report a major update of the MAFFT multiple sequence alignment program. This version has several new features, including options for adding unaligned sequences into an existing alignment, adjustment of direction in nucleotide alignment, constrained alignment and parallel processing, which were implemented after the previous major update. This report shows actual examples to explain how these features work, alone and in combination. Some examples incorrectly aligned by MAFFT are also shown to clarify its limitations. We discuss how to avoid misalignments, and our ongoing efforts to overcome such limitations.
Article
Full-text available
Analysis of codon usage can reveal much about the molecular evolution of the viruses. Nevertheless, little information about synonymous codon usage pattern of porcine circovirus (PCV) genome in the process of its evolution is available. In this study, to give a new understanding on the evolutionary characteristics of PCV and the effects of natural selection from its host on the codon usage pattern of the virus, Patterns and the key determinants of codon usage in PCV were examined. We carried out comprehensive analysis on codon usage pattern in the PCV genome, by calculating relative synonymous codon usage (RSCU), effective number of codons (ENC), dinucleotides and nucleic acid content of the PCV genome. PCV genomes have relatively much lower content of GC and codon preference, this result shows that nucleotide constraints have a major impact on its synonymous codon usage. The results of the correspondence analysis indicate codon usage patterns of PCV of various genotypes, various subgenotypes changed greatly, and significant differences in codon usage patterns of Each virus of Circoviridae.There is much comparability between PCV and its host in their synonymous codon usage, suggesting that the natural selection pressure from the host factor also affect the codon usage patterns of PCV. In particular, PCV genotype II is in synonymous codon usage more similar to pig than to PCV genotype I, which may be one of the most important molecular mechanisms of PCV genotype II to cause disease. The calculations results of the relative abundance of dinucleotides indicate that the composition of dinucleotides also plays a key role in the variation found in synonymous codon usage in PCV. Furthermore, geographic factors, the general average hydrophobicity and the aromaticity may be related to the formation of codon usage patterns of PCV. The results of these studies suggest that synonymous codon usage pattern of PCV genome are the result of interaction between mutation pressure and natural selection from its host. The information from this study may not only have theoretical value in understanding the characteristics of synonymous codon usage in PCV genomes, but also have significant value for the molecular evolution of PCV.
Article
Full-text available
Over the past 30 years, several cross-species transmission events, as well as changes in virus tropism, have mediated significant animal and human diseases. Most notable is severe acute respiratory syndrome (SARS), a lower respiratory tract disease of humans that was first reported in late 2002 in Guangdong Province, China. The disease, which quickly spread worldwide over a period of 4 months spanning late 2002 and early 2003, infected over 8,000 individuals and killed nearly 800 before it was successfully contained by aggressive public health intervention strategies. A coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and initial assessments determined that the virus crossed to human hosts from zoonotic reservoirs, including bats, Himalayan palm civets (Paguma larvata), and raccoon dogs (Nyctereutes procyonoides), sold in exotic animal markets in Guangdong Province. In this review, we discuss the molecular mechanisms that govern coronavirus cross-species transmission both in vitro and in vivo, using the emergence of SARS-CoV as a model. We pay particular attention to how changes in the Spike attachment protein, both within and outside of the receptor binding domain, mediate the emergence of coronaviruses in new host populations.
Article
Full-text available
Viruses differ markedly in their specificity toward host organisms. Here, we test the level of general sequence adaptation that viruses display toward their hosts. We compiled a representative data set of viruses that infect hosts ranging from bacteria to humans. We consider their respective amino acid and codon usages and compare them among the viruses and their hosts. We show that bacteria-infecting viruses are strongly adapted to their specific hosts, but that they differ from other unrelated bacterial hosts. Viruses that infect humans, but not those that infect other mammals or aves, show a strong resemblance to most mammalian and avian hosts, in terms of both amino acid and codon preferences. In groups of viruses that infect humans or other mammals, the highest observed level of adaptation of viral proteins to host codon usages is for those proteins that appear abundantly in the virion. In contrast, proteins that are known to participate in host-specific recognition do not necessarily adapt to their respective hosts. The implication for the potential of viral infectivity is discussed.
Article
Full-text available
We investigated genetic recombination of the human immunodeficiency virus (HIV) in a tissue culture system. A clonal cell line expressing a single integrated HIV provirus with a termination codon affecting pol gene expression was transfected with different defective mutants derived from an infectious molecular clone of HIV. Replication-competent viral particles were recovered, passaged, and plaque purified. Restriction analyses of the proviral DNA corresponding to several of these viruses indicated that their emergence was the result of genetic recombination.
Article
Full-text available
The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env, nef, and the 3' long terminal repeat as determined by both maximal chi2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.
Article
Full-text available
Recombination events are known to occur in non-segmented RNA viruses like polioviruses or alphaviruses. Analysis of the subgenomic sequences of dengue virus type 1 (DENV-1) structural genes has recently allowed the identification of possible recombination breakpoints. Because DENV is a major human pathogen, this discovery might have important implications for virus pathogenicity, vaccine safety and efficiency, or diagnosis and, therefore, requires clear confirmation. We report the complete sequence determination of one Asian and two African strains of DENV-1 isolated from human patients. Rigorous sequence analysis provided strong evidence for the occurrence of intragenomic recombination events between DENV-1 strains belonging to different lineages. Singapore S275/90 strain appears to be the evolutionary product of a recombination event between viruses belonging to two distinct lineages: one lineage includes an African strain isolated in Abidjan (Ivory Coast) and the other includes isolates from Djibouti and Cambodia. The 'Recombination Detection Program', bootscanning and analysis of diversity plots provided congruent results concerning the existence of a two-switch recombination event and the localization of recombination breakpoints. Thus, the 5' and 3' genomic ends of the Singapore S275/90 strain were inherited from a Djibouti/Cambodia lineage ancestor and an internal fragment located in the envelope/NS1 region originated from an Abidjan lineage ancestor.
Article
Full-text available
A novel coronavirus (SCoV) is the etiological agent of severe acute respiratory syndrome (SARS). SCoV-like viruses were isolated from Himalayan palm civets found in a live-animal market in Guangdong, China. Evidence of virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the same market. All the animal isolates retain a 29-nucleotide sequence that is not found in most human isolates. The detection of SCoV-like viruses in small, live wild mammals in a retail market indicates a route of interspecies transmission, although the natural reservoir is not known.
Article
Full-text available
Hepatitis C virus (HCV) has high genomic variability and, since its discovery, at least six different types and an increasing number of subtypes have been reported. Genotype 1 is the most prevalent genotype found in South America. In the present study, three different genomic regions (5'UTR, core and NS5B) of four HCV strains isolated from Peruvian patients were sequenced in order to investigate the congruence of HCV genotyping for these three genomic regions. Phylogenetic analysis using 5'UTR-core sequences found strain PE22 to be related to subtype 1b. However, the same analysis using the NS5B region found it to be related to subtype 1a. To test the possibility of genetic recombination, phylogenetic studies were carried out, revealing that a crossover event had taken place in the NS5B protein. We discuss the consequences of this observation on HCV genotype classification, laboratory diagnosis and treatment of HCV infection.
Article
Respiratory tract viral infection caused by viruses or bacteria is one of the most common diseases in human worldwide, while those caused by emerging viruses, such as the novel coronavirus, 2019‐nCoV that caused the pneumonia outbreak in Wuhan, China most recently, have posed great threats to global public health. Identification of the causative viral pathogens of respiratory tract viral infections is important to select an appropriate treatment, save people's lives, stop the epidemics, and avoid unnecessary use of antibiotics. Conventional diagnostic tests, such as the assays for rapid detection of antiviral antibodies or viral antigens, are widely used in many clinical laboratories. With the development of modern technologies, new diagnostic strategies, including multiplex nucleic acid amplification and microarray‐based assays, are emerging. This review summarizes currently available and novel emerging diagnostic methods for the detection of common respiratory viruses, such as influenza virus, human respiratory syncytial virus, coronavirus, human adenovirus, and human rhinovirus. Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. It is anticipated that such data will assist researchers and clinicians to develop appropriate diagnostic strategies for timely and effective detection of respiratory virus infections. Research Highlights • Respiratory tract viral infection including 2019‐nCoV poses great threats worldwide. Currently available and novel emerging diagnostic methods are summarized for several common respiratory viruses, including influenza virus, human respiratory syncytial virus, coronavirus, human adenovirus and human rhinovirus. Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. This review is aimed to assist researchers and clinicians to develop timely and effective diagnostic strategies to detect respiratory virus infections.
Article
With increased globalisation comes the likelihood that infectious disease appearing in one country will spread rapidly to another, severe acute respiratory syndrome (SARS) being a recent example. However, although SARS infected some 10,000 individuals, killing around 1000, it did not lead to the devastating health impact that many feared, but a rather disproportionate economic impact. The disproportionate scale and nature of this impact has caused concern that outbreaks of more serious disease could cause catastrophic impacts on the global economy. Understanding factors that led to the impact of SARS might help to deal with the possible impact and management of such other infectious disease outbreaks. In this respect, the role of risk-its perception, communication and management-is critical. This paper looks at the role that risk, and especially the perception of risk, its communication and management, played in driving the economic impact of SARS. It considers the public and public health response to SARS, the role of the media and official organisations, and proposes policy and research priorities for establishing a system to better deal with the next global infectious disease outbreak. It is concluded that the potential for the rapid spread of infectious disease is not necessarily a greater threat than it has always been, but the effect that an outbreak can have on the economy is, which requires further research and policy development.
Article
Citrus exocortis viroid (CEV) is widespread in citrus production areas where trifoliate orange [Poncirus trifoliata (L.) Raf.] is used as rootstock. Citrus reticulata Blanco cv. Red tangerine, a different rootstock, is tolerant to CEV. Embryogenic protoplasts of C. reticulata cv. Red tangerine were electrically fused with mesophyll protoplasts from P. trifoliata, and five embryoids were regenerated after 40 days of culture. The embryoids were cut into several pieces and subcultured on shoot induction medium. After 5 months and several subcultures, shoots initially regenerated. The plants grew vigorously with well-developed root systems and exhibited the trifoliate leaf character of P. trifoliata. Chromosome counts on four randomly selected root tips revealed them to be tetraploids (2n=4x=36). RAPD analysis of four randomly selected plants verified their hybridity. This hybridity was further confirmed by AFLP analysis using four primer pairs, from which a total of 65 specific bands were detected. Cytoplasmic genome analysis using universal primers revealed that their chloroplast DNA banding pattern was identical to that of trifoliate orange, while the banding pattern of mitochondrial DNA was identical to that of Red tangerine. The potential of this somatic hybrid as a means to control tree size and provide multi-resistance is discussed.
Article
Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an unknown cause. Infection with Anaplasma phagocytophilum has been suggested as a cause, but the pathogen has not been detected in most patients on laboratory testing. We obtained blood samples from patients with the case definition of SFTS in six provinces in China. The blood samples were used to isolate the causal pathogen by inoculation of cell culture and for detection of viral RNA on polymerase-chain-reaction assay. The pathogen was characterized on electron microscopy and nucleic acid sequencing. We used enzyme-linked immunosorbent assay, indirect immunofluorescence assay, and neutralization testing to analyze the level of virus-specific antibody in patients' serum samples. We isolated a novel virus, designated SFTS bunyavirus, from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction. RNA sequence analysis revealed that the virus was a newly identified member of the genus phlebovirus in the Bunyaviridae family. Electron-microscopical examination revealed virions with the morphologic characteristics of a bunyavirus. The presence of the virus was confirmed in 171 patients with SFTS from six provinces by detection of viral RNA, specific antibodies to the virus in blood, or both. Serologic assays showed a virus-specific immune response in all 35 pairs of serum samples collected from patients during the acute and convalescent phases of the illness. A novel phlebovirus was identified in patients with a life-threatening illness associated with fever and thrombocytopenia in China. (Funded by the China Mega-Project for Infectious Diseases and others.).
Article
A simple measure is presented that quantifies how far the codon usage of a gene departs from equal usage of synonymous codons. This measure of synonymous codon usage bias, the 'effective number of codons used in a gene', Nc, can be easily calculated from codon usage data alone, and is independent of gene length and amino acid (aa) composition. Nc can take values from 20, in the case of extreme bias where one codon is exclusively used for each aa, to 61 when the use of alternative synonymous codons is equally likely. Nc thus provides an intuitively meaningful measure of the extent of codon preference in a gene. Codon usage patterns across genes can be investigated by the Nc-plot: a plot of Nc vs. G + C content at synonymous sites. Nc-plots are produced for Homo sapiens, Saccharomyces cerevisiae, Escherichia coli, Bacillus subtilis, Dictyostelium discoideum, and Drosophila melanogaster. A FORTRAN77 program written to calculate Nc is available on request.
Article
A comparison of 25 hepatitis B virus (HBV) isolates for which complete genome sequences are available revealed two that occupied different positions in phylogenetic trees reconstructed from different open reading frames. Further analysis indicated that this incongruence was the result of recombination between viruses of different genomic and antigenic types. Both putative recombinants originated from geographic regions where multiple genotypes are known to cocirculate. A search of the sequence databases showed evidence of similar intergenotypic recombinants. These observations indicate that recombination between divergent strains may represent an important source of genetic variation in HBV.
Article
The first outbreak of avian influenza A(H5N1) virus in humans occurred in Hong Kong in 1997. Infection was confirmed in 18 individuals, 6 of whom died. Infections were acquired by humans directly from chickens, without the involvement of an intermediate host. The outbreak was halted by a territory-wide slaughter of more than 1.5 million chickens at the end of December 1997. The clinical spectrum of H5N1 infection ranges from asymptomatic infection to fatal pneumonitis and multiple organ failure. Reactive hemophagocytic syndrome was the most characteristic pathologic finding and might have contributed to the lymphopenia, liver dysfunction, and abnormal clotting profiles that were observed among patients with severe infection. Rapid diagnosis with the use of reverse-transcription polymerase chain reaction and monoclonal antibody-based immunofluorescent assay were of great clinical value in the management of the outbreak. The experience of the H5N1 outbreak in Hong Kong underscores the importance of continuous surveillance of influenza virus strains in humans and in other animal species.
Article
With increased globalisation comes the likelihood that infectious disease appearing in one country will spread rapidly to another, severe acute respiratory syndrome (SARS) being a recent example. However, although SARS infected some 10,000 individuals, killing around 1000, it did not lead to the devastating health impact that many feared, but a rather disproportionate economic impact. The disproportionate scale and nature of this impact has caused concern that outbreaks of more serious disease could cause catastrophic impacts on the global economy. Understanding factors that led to the impact of SARS might help to deal with the possible impact and management of such other infectious disease outbreaks. In this respect, the role of risk--its perception, communication and management--is critical. This paper looks at the role that risk, and especially the perception of risk, its communication and management, played in driving the economic impact of SARS. It considers the public and public health response to SARS, the role of the media and official organisations, and proposes policy and research priorities for establishing a system to better deal with the next global infectious disease outbreak. It is concluded that the potential for the rapid spread of infectious disease is not necessarily a greater threat than it has always been, but the effect that an outbreak can have on the economy is, which requires further research and policy development.
Biomedical Informatics for Cancer Research
  • H Howe
  • K Holton
  • S Nair
  • D Schlauch
  • R Sinha
  • J Quackenbush
Middle East respiratory syndrome (MERS) A new zoonotic viral pneumonia
  • CB Cunha
  • SM Opal
How to cite this article
  • W Ji
  • W Wang
  • X Zhao
  • J Zai
  • X Li
How to cite this article: Ji W, Wang W, Zhao X, Zai J, Li X.
Cross-species transmission of the newly identified coronavirus 2019-nCoV
Cross-species transmission of the newly identified coronavirus 2019-nCoV. J Med Virol. 2020;92: 433-440. https://doi.org/10.1002/jmv.25682