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Bats and Coronaviruses
Abstract
Bats are speculated to be reservoirs of several emerging viruses including coronaviruses (CoVs) that cause serious disease in humans and agricultural animals. These include CoVs that cause severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), porcine epidemic diarrhea (PED) and severe acute diarrhea syndrome (SADS). Bats that are naturally infected or experimentally infected do not demonstrate clinical signs of disease. These observations have allowed researchers to speculate that bats are the likely reservoirs or ancestral hosts for several CoVs. In this review, we follow the CoV outbreaks that are speculated to have originated in bats. We review studies that have allowed researchers to identify unique adaptation in bats that may allow them to harbor CoVs without severe disease. We speculate about future studies that are critical to identify how bats can harbor multiple strains of CoVs and factors that enable these viruses to “jump” from bats to other mammals. We hope that this review will enable readers to identify gaps in knowledge that currently exist and initiate a dialogue amongst bat researchers to share resources to overcome present limitations.
... The term corona virus (Latin: Corona, crown) is coined due to presence of spikes glycoproteins on the surface that gives it a crown-like appearance. Coronaviruses came from the family Coronaviridae and the order Nidovirales [5]. This virus broadly distributed in several mammals including humans, with a large Positive-sense RNA encapsulated in a protein coat. ...
... Additionally, drug repositioning has also been approved to be effective for COVID -19 patients [5]. ...
The term corona virus (Latin: Corona, crown) is coined due to presence of spikes glycoproteins on the surface that gives it a crown-like appearance. Coronaviruses came from the family Coronaviridae and the order Nidovirales. Novel Corona Virus Disease outbreak happened in January 2020 subsequently dispersed around the world and reason for death of several million people worldwide. Currently, no effective treatment for severe COVID-19 patients is present. Now days, patients are only treated symptomatically. Scientific community working to develop novel antiviral drugs, vaccines, immunomodulatory medications. In the recent scenario of COVID-19 pandemic, we lack any better therapeutic option for treatment of severe COVID-19 patients. MSCs may be a better option for providing emergency therapy. Vast number of studies and clinical trials are warranted regarding the safety and efficacy stem cell therapy in COVID-19 and other respiratory disorders.
... The Duvinacovirus sub-genus comprises the Hu-CoV 229E strain known to induce common cold in humans [32]. This virus originates from bats and more specifically from Hipposideros species [3]. ...
... We also identified a CoV clade belonging to the Setracovirus sub-genus together with the Hu-CoV NL63 strain which also induces common cold in humans [32]. To date NL63related bat CoV have been identified to originate from the Triaenop bat genus [43]. ...
Background:
Studies have linked bats to outbreaks of viral diseases in human populations such as SARS-CoV-1 and MERS-CoV and the ongoing SARS-CoV-2 pandemic.
Methods:
We carried out a longitudinal survey from August 2020 to July 2021 at two sites in Zimbabwe with bat-human interactions: Magweto cave and Chirundu farm. A total of 1732 and 1866 individual bat fecal samples were collected, respectively. Coronaviruses and bat species were amplified using PCR systems.
Results:
Analysis of the coronavirus sequences revealed a high genetic diversity, and we identified different sub-viral groups in the Alphacoronavirus and Betacoronavirus genus. The established sub-viral groups fell within the described Alphacoronavirus sub-genera: Decacovirus, Duvinacovirus, Rhinacovirus, Setracovirus and Minunacovirus and for Betacoronavirus sub-genera: Sarbecoviruses, Merbecovirus and Hibecovirus. Our results showed an overall proportion for CoV positive PCR tests of 23.7% at Chirundu site and 16.5% and 38.9% at Magweto site for insectivorous bats and Macronycteris gigas, respectively.
Conclusions:
The higher risk of bat coronavirus exposure for humans was found in December to March in relation to higher viral shedding peaks of coronaviruses in the parturition, lactation and weaning months of the bat populations at both sites. We also highlight the need to further document viral infectious risk in human/domestic animal populations surrounding bat habitats in Zimbabwe.
... Bats that are naturally infected or experimentally infected do not show any signs of disease. (Banerjee et al., 2019). ...
... and posed in 8,098 confirmed human cases globally, of which 774 (9.5%) were fatal. Approximately ten years after SARS-CoV, a new highly pathogenic human coronavirus occurred in Saudi Arabia, called"Middle East respiratory syndrome coronavirus" (MERS-CoV). MERS-CoV has resulted in a total of 2,260 confirmed cases in 27 countries, of which 803 died.(Banerjee, Kulcsar, Misra, Frieman, & Mossman, 2019). ...
Text is the main method of communicating information in the digital age. Applications, Messages, blogs, news articles, reviews, and opinionated information abounds on the Internet. People commonly purchase applications and post their opinions about purchased items. This feedback is displayed publicly to assist others when making decisions, creating a mechanism to extract and summarize useful information to
enhance the decision-making process. Our contribution is to improve the accuracy of extraction by combining different techniques from three major areas, named Data Mining,
Natural Language Processing techniques and Ontologies of these applications. The proposed framework sequentially mines applications’ aspects and users’ opinions, groups
representative aspects by similarity, and generates an output summary. This paper focuses on application reviews based on users’ opinions by extracting all possible aspects and opinions from reviews using natural language, ontology and frequent “tag” sets. The proposed framework, when compared with an existing baseline model, yields promising results
... The majority of coronaviruses are linked to infections of the upper and lower respiratory tract (Vabret et al., 2008;Owusu et al., 2014). Coronaviruses are most likely to have their origins in bats (Wang et al., 2006;Acter et al., 2020;Banerjee et al., 2019). Zoonotic transmission of these viruses can occur via the civets and dromedary camels (Ye et al., 2020). ...
... Coronaviruses are enveloped single stranded RNA viruses belonging to the Genus Coronavirus (alpha, beta, gamma or delta) to infect humans and animals (Mattar and González, 2018). The primary reservoirs of these viruses are most likely bats (Wang et al., 2006; Banerjee et al., 2019). Cats and camels may be involved in the transmission cycle of these viruses (Ye et al., 2020). ...
This study aimed to investigate the prevalence of COVID-19 in domestic cats, focusing on the disease in the north-west of Iran and then showing the natural transmission of SARS-COV-2 circulating between domestic cats and humans.
After receiving ethic codes from Tehran University of Medical Sciences (IR.TUMS.VCR.REC.1399.303) and confirmed by the Center of Communicable Diseases Control (CDC) of Iran, 124 domestic cats were collected from the homes and only one hospital of Meshkin -Shahr district from northwestern Iran where SARS-CoV-2 patients were hospitalized and quarantined during 2020. Samples were prepared from fluid materials of oropharynx and nasopharynx. All samples were tested by real-time PCR (RT-PCR) using specific genes N and ORF1ab in Pasteur Institute of Iran, and then partial sequence analyses of S gene were performed. All collected cats were kept in separated cages until SARS-COV-2 infection was confirmed with the RT-PCR.
RT- PCR Ct values of 123 collected cats were ≥40; thus, all of them showed negative results, but one of the collected cats with close contact with its owner, whom confirmed SARS-CoV-2 showed positive results with gene N(Ct=30) and gene ORF1ab (Ct=32). Furthermore, the positive pet cat showed respiratory and gastro-intestinal clinical manifestations, and its owner was infected with SARS-CoV-2 two weeks ago.
Cats are susceptible animals to SARS-CoV-2 infection. Epidemiological evidence showed that SARS-COV-2 is able to transmit to healthy cats due to having close contact with its owner as a reverse zoonosis.
... The 21st century has seen a series of public health emergencies caused by zoonotic coronavirus (CoV) diseases: the SARS epidemic in 2002-2003, periodic MERS outbreaks since 2012, and the ongoing COVID-19 pandemic [1]. Given ever-increasing human contact with major CoV reservoirs such as bats [2] due to habitat encroachment and climate change, novel CoV diseases will likely continue to emerge in the near future, generating new public health challenges. It is therefore urgent to identify anti-viral therapeutics that are effective against a broad spectrum of CoVs, especially CoVs derived from bats, which are thought to have been the source of the previous 21st-century CoV zoonoses and are one of the most likely sources for future novel CoVs [2,3]. ...
... Given ever-increasing human contact with major CoV reservoirs such as bats [2] due to habitat encroachment and climate change, novel CoV diseases will likely continue to emerge in the near future, generating new public health challenges. It is therefore urgent to identify anti-viral therapeutics that are effective against a broad spectrum of CoVs, especially CoVs derived from bats, which are thought to have been the source of the previous 21st-century CoV zoonoses and are one of the most likely sources for future novel CoVs [2,3]. To date, however, no drugs proven to be effective against a broad spectrum of CoVs have been identified. ...
Recurrent outbreaks of novel zoonotic coronavirus (CoV) diseases in recent years have highlighted the importance of developing therapeutics with broad-spectrum activity against CoVs. Because all CoVs use −1 programmed ribosomal frameshifting (−1 PRF) to control expression of key viral proteins, the frameshift signal in viral mRNA that stimulates −1 PRF provides a promising potential target for such therapeutics. To test the viability of this strategy, we explored whether small-molecule inhibitors of −1 PRF in SARS-CoV-2 also inhibited −1 PRF in a range of bat CoVs—the most likely source of future zoonoses. Six inhibitors identified in new and previous screens against SARS-CoV-2 were evaluated against the frameshift signals from a panel of representative bat CoVs as well as MERS-CoV. Some drugs had strong activity against subsets of these CoV-derived frameshift signals, while having limited to no effect on −1 PRF caused by frameshift signals from other viruses used as negative controls. Notably, the serine protease inhibitor nafamostat suppressed −1 PRF significantly for multiple CoV-derived frameshift signals. These results suggest it is possible to find small-molecule ligands that inhibit −1 PRF specifically in a broad spectrum of CoVs, establishing frameshift signals as a viable target for developing pan-coronaviral therapeutics.
... The term coronavirus (Latin: corona, crown) is coined due to presence of spikes glycoproteins on the surface that gives this virus a crown-like appearance. Coronaviruses belong to the family Coronaviridae and the order Nidovirales [1], broadly distributed in humans and other mammals, having a large positive-sense RNA encapsulated within a protein coat. Coronaviruses majorly affect animals and display zoonotic transmission from animals to humans. ...
... This outbreak had 2260 confirmed cases and 803 reported deaths. It targets the upper respiratory tract and causes severe respiratory distress [1]. At present, the whole world is experiencing an outbreak due to a novel strain of coronavirus named as SARS-CoV-2 and the resultant disease called as COVID-19. ...
The novel virus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) caused the Corona Virus Disease-2019 (COVID-19) outbreak in Wuhan, Hubei province of China. This virus disseminated rapidly and reached to an unprecedented pandemic proportion in more than 213 nations with a large number of fatalities. The hypersecretion of pro-inflammatory cytokines is the main cause of mortality and morbidity due to COVID-19, therefore strategies that avert the cytokine storm may play a crucial role in abating the severity of COVID-19. This review highlights the minute details of SARS-CoV-2, its genomic organization, genomic variations within structural and non-structural proteins and viral progression mechanism in human beings. The approaches like antiviral strategies are discussed, including drugs that obstruct viral propagation and suppress the pro-inflammatory cytokines. This compilation emphasizes Mesenchymal Stem Cells (MSCs) based therapy alone or in combination with other therapeutics as an attractive curative approach for COVID-19 pandemic. The MSCs and its secretome, including antimicrobial peptides (AMPs) have various capabilities, for instance, immunomodulation, regeneration, antimicrobial properties, potential for attenuating the cytokine storm and bare minimum chances of being infected with SARS-CoV-2 virus. The immunomodulatory property of MSCs affects inflammatory state and regulates immune response during SARS-CoV-2 infection. However, as of now, there is no WHO-approved MSCs based therapy for the treatment of COVID-19 infection.
... Throughout the 21st century, HCoV's have been identified in various locations worldwide and were correlated with outbreaks of deadly human pneumonia . The first CoV outbreak was reported in November 2002 in Foshan, China, causing severe acute respiratory syndrome (SARS-CoV) (Banerjee et al., 2019). In 2003, the outbreak spread into a global infection with a 10% mortality rate . ...
... Currently, the diagnosis of SARS-CoV-2 is based on the detection of viral nucleic acids, antibodies, and proteins. Still, the real-time polymerase chain reaction (RT-PCR) remains the gold standard in diagnosing COVID-19 (Banerjee et al., 2019). Diagnosis based on nucleic acid detection is more sensitive and specific than currently available serological tests. ...
In late December 2019, the first cases of viral pneumonia caused by an unidentified pathogen were reported in China. Two years later, SARS-CoV-2 was responsible for almost 450 million cases, claiming more than 6 million lives. The COVID-19 pandemic strained the limits of healthcare systems all across the world. Identifying viral RNA through real-time reverse transcription-polymerase chain reaction remains the gold standard in diagnosing SARS-CoV-2 infection. However, equipment cost, availability, and the need for trained personnel limited testing capacity. Through an unprecedented research effort, new diagnostic techniques such as rapid diagnostic testing, isothermal amplification techniques, and next-generation sequencing were developed, enabling accurate and accessible diagnosis. Influenza viruses are responsible for seasonal outbreaks infecting up to a quarter of the human population worldwide. Influenza and SARS-CoV-2 present with flu-like symptoms, making the differential diagnosis challenging solely on clinical presentation. Healthcare systems are likely to be faced with overlapping SARS-CoV-2 and Influenza outbreaks. This review aims to present the similarities and differences of both infections while focusing on the diagnosis. We discuss the clinical presentation of Influenza and SARS-CoV-2 and techniques available for diagnosis. Furthermore, we summarize available data regarding the multiplex diagnostic assay of both viral infections.
... The corona virus-classified into α-and β-subtypes that infect mammals, and γ-and δ-subtypes that infect birds and pigs-was first reported by Tyrell and Bonne in 1996 from the patients suffering common cold [2][3][4] . The twothirds of its 26-32 kb genome encodes viral polymerase, RNA synthesis materials, and two large non-structural polyproteins whereas one-third of the genome codes for the envelope, membrane, nucleocapsid (N), and helper proteins by proteolysis of a common polypeptide chain [3][4][5][6] . ...
... The corona virus-classified into α-and β-subtypes that infect mammals, and γ-and δ-subtypes that infect birds and pigs-was first reported by Tyrell and Bonne in 1996 from the patients suffering common cold [2][3][4] . The twothirds of its 26-32 kb genome encodes viral polymerase, RNA synthesis materials, and two large non-structural polyproteins whereas one-third of the genome codes for the envelope, membrane, nucleocapsid (N), and helper proteins by proteolysis of a common polypeptide chain [3][4][5][6] . Proteases thus play important roles in viral replication and therefore identifies itself as a possible target for anti-COVID-19 inhibitors 7 . ...
SARS-CoV-2 the new strain of SARS corona virus is an RNA virus that inflicts acute respiratory distress syndrome due to infection of the alveolar epithelial cells, its primary target. No effective drug is currently available to treat this viral infection. Therefore, we focused on identifying inhibitors of the main viral protease domain (Mpro) which plays important role in the virus life cycle. Two tired computer-aided drug discovery approach were adopted for screening of novel inhibitors against Mpro, the target protein. First, based on their ADME/T properties, phytochemicals as well as synthetic drugs six compounds were selected from the available database. In second screening by molecular docking based on binding affinity and molecular interactions of these compounds with Mpro led to the identification of the best phytochemical and synthetic compound against Mpro. The result of docking complex showed that, interacting residues for myricetin are continuous while, in case of fosamprenavir, these are non-contiguous. Both molecules interact with the residues in the active site occupying the site for the catalytic activity indicate possible competitive inhibitors of the Mpro.
... In the past 20 years, bat-derived coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 have been responsible for two deadly epidemics and the ongoing COVID-19 pandemic (1)(2)(3)(4). These coronaviruses (CoVs) are members of the Betacoronavirus genus, which, along with genus Alphacoronavirus, are primarily associated with bat hosts (1)(2)(3)(4); the remaining CoV genera, Gammacoronavirus and Deltacoronavirus, are typically hosted by birds (5). ...
... In the past 20 years, bat-derived coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 have been responsible for two deadly epidemics and the ongoing COVID-19 pandemic (1)(2)(3)(4). These coronaviruses (CoVs) are members of the Betacoronavirus genus, which, along with genus Alphacoronavirus, are primarily associated with bat hosts (1)(2)(3)(4); the remaining CoV genera, Gammacoronavirus and Deltacoronavirus, are typically hosted by birds (5). The Betacoronavirus group can be further broken down into five subgenera: Sarbecovirus [hosted by bats in family Rhinolophidae (6,7)], Merbecovirus [hosted by bats in family Vespertilionidae (8)(9)(10)], Nobecovirus [hosted by bats in family Pteropodidae (11)(12)(13)], and Hibecovirus [hosted by bats in family Hipposideridae (14)(15)(16)]. ...
Bats are natural reservoirs for both Alpha - and Betacoronaviruses and the hypothesized original hosts of five of seven known zoonotic coronaviruses. To date, the vast majority of bat coronavirus research has been concentrated in Asia, though coronaviruses are globally distributed; indeed, SARS-CoV and SARS-CoV-2-related Betacoronaviruses in the subgenus Sarbecovirus have been identified circulating in Rhinolophid bats in both Africa and Europe, despite the relative dearth of surveillance in these regions. As part of a long-term study examining the dynamics of potentially zoonotic viruses in three species of endemic Madagascar fruit bat ( Pteropus rufus, Eidolon dupreanum, Rousettus madagascariensis ), we carried out metagenomic Next Generation Sequencing (mNGS) on urine, throat, and fecal samples obtained from wild-caught individuals. We report detection of RNA derived from Betacoronavirus subgenus Nobecovirus in fecal samples from all three species and describe full genome sequences of novel Nobecoviruses in P. rufus and R. madagascariensis . Phylogenetic analysis indicates the existence of five distinct Nobecovirus clades, one of which is defined by the highly divergent ancestral sequence reported here from P. rufus bats. Madagascar Nobecoviruses derived from P. rufus and R. madagascariensis demonstrate, respectively, Asian and African phylogeographic origins, mirroring those of their fruit bat hosts. Bootscan recombination analysis indicates significant selection has taken place in the spike, nucleocapsid, and NS7 accessory protein regions of the genome for viruses derived from both bat hosts. Madagascar offers a unique phylogeographic nexus of bats and viruses with both Asian and African phylogeographic origins, providing opportunities for unprecedented mixing of viral groups and, potentially, recombination. As fruit bats are handled and consumed widely across Madagascar for subsistence, understanding the landscape of potentially zoonotic coronavirus circulation is essential for mitigation of future zoonotic threats.
... Climate change aAects global diversity (Beyer et al. 2021). Bats are the probable zoonotic cause of both SARS-CoV-1 and SAR-CoV-2 (recognized as COVID-19 pandemic), which result in severe critical respiratory syndrome from wildlife (agricultural animals) to humans (Banerjee et al. 2019;Beyer et al. 2021;Xiao et al. 2020), indicating a link between BC and Coronavirus. The number of CoVs numbers existing in a region is strongly linked with native bat species, and is inCuenced by climatic situations that drive species' geographical dispersals (Beyer et al. 2021). ...
... BC is the next most climate driving agent present in the atmosphere after CO 2 (Ramanathan and Carmichael 2008). Climate change might cause the evolution and spread of the two SARS coronaviruses (CoVs) (Banerjee et al. 2019). ...
The COVID-19 epidemic-led lockdown (LD) from March 25 to May 31, 2020, had a different level of impact on air quality in the ecologically sensitive region of northeast India, even though the restriction on main anthropogenic activities was expected to reduce particulate matter concentration. The daily average black carbon concentration measured at 880 nm (BC880) was 1.5–15.6 μg m−3 (mean: 5.75±4.24 μg m−3) during the measurement period. It was 9.29±4.11 μg m−3 during pre-LD (February 12–March 21), 4.70±0.95 μg m−3 during LD1 (March 25–April 14), 3.41±0.56 μg m−3 during LD2 (April 15–May 3), 3.69±1.50 μg m−3 during LD3 (May 4–17), 2.94±0.93 μg m−3 during LD4 (May 18–31), and 6.56±5.35 μg m−3 during the Post-LD (June 6–July 3) of 2020. It decreased up to 68% during the lockdowns. The source apportionment based on an improved method showed a significant improvement in the contribution of BC880 sources. The radiation effect determined by Angstrom Absorption Exponent showed that brown carbon accounted for 25% of the aerosol light absorption at 370 nm during the lockdown period. Relative humidity correlates substantially with BC880, while rainfall, temperature, and solar radiation were negatively correlated. The bivariate analysis showed the dominance of local emissions in the BC880 concentrations.
... The disease emerged in Wuhan, China, and has become a pandemic (Shereen et al. 2020). Studies have shown that Open Access severe acute respiratory syndrome-like viruses (found in bats) are phylogenetically linked, and hence, bats could be the principal reservoir for SARS COV2 (Banerjee et al. 2019;Boni et al. 2020;Shereen et al. 2020). Epidemiologically, COVID-19 is currently a major pandemic with over 5.8 million deaths reported as of 15 February 2022 globally, which is of great concern (WHO Report 2022). ...
Background
A common complication of any respiratory disease by a virus could be a secondary bacterial infection, which is known to cause an increase in severity. It is, however, not clear whether the presence of some opportunistic pathogens called pathobionts contributes to the severity of the disease. In COVID-19 patients, undetected bacterial co-infections may be associated with the severity of the disease. Therefore, we investigated the implications of bacterial co-infections in COVID-19 cases.
Results
This is a cross-sectional study that involved archived specimens collected from nasopharyngeal samples of 150 people for COVID-19 screening in Lagos. DNA extraction from the samples was carried out to determine the presence of five respiratory bacterial pathogens using nested real-time PCR, and data were analysed using the Chi-square test. Of the 150 samples collected, 121 (80.7%) were positive for SARs-CoV-2 infection and 29 were negative. The proportion of patients with bacteria co-infection in COVID-19-negative, asymptomatic, and mild cases were 93.1%, 70.7%, and 67.5%, respectively. There was no statistically significant difference between mild COVID-19 conditions and bacteria co-infection ( p = 0.097). There was also no significant difference in the nasal carriage of Staphylococcus aureus , Mycoplasma pneumoniae , and Haemophilus spp. However, there was a statistically significant increase in the carriage of Moraxella catarrhalis and Chlamydophila pneumoniae among COVID-19-negative patients when compared with the positive patients ( p value = 0.003 and 0.000 for Moraxella catarrhalis and Chlamydophila pneumoniae , respectively).
Conclusions
The current study shows that bacterial co-infection and superinfection with COVID-19 are not associated with mild and asymptomatic COVID-19 cases in our setting. However, given the high prevalence of Staphylococcus aureus and Mycoplasma pneumoniae among the mild COVID-19 cases seen in this study, early diagnosis and treatment of these bacterial co-infections are still encouraged to mitigate the effect on the severity of COVID-19.
... The human coronaviruses (HCoVs) are members of the coronaviruses family, and responsible for multiple respiratory conditions including the common cold, bronchiolitis and pneumonia 3 . HCoVs periodically appear in different places around the world and have been linked with epidemic or pandemic human pneumonia since the beginning of the 21 st century 4 ; they include the severe acute respiratory syndrome coronavirus (SARS-CoV), in November 2002, and the Middle East respiratory syndrome coronavirus (MERS-CoV) in June 2012 5 . ...
Il rischio di contagio da SARS-CoV-2 tra gli specialisti in otorinolaringoiatria.
Riassunto: La malattia da COVID-19 si è rapidamente diffusa negli ultimi due anni con un forte impatto sull’attività otorinolaringoiatrica, che ha subito una radicale trasformazione per garantire assistenza principalmente a pazienti oncologici e urgenti, e assicurare protezione al personale sanitario e ai pazienti. Durante le fasi iniziali della pandemia, le visite programmate e gli interventi chirurgici elettivi sono stati posticipati, spesso causando un ritardo nella diagnosi e nel trattamento di diverse condizioni, anche oncologiche, con diagnosi in fasi di malattia avanzata e trattamenti più aggressivi. L’aerosol e le goccioline di saliva sono la principale via di trasmissione del virus SARS-CoV-2. Pertanto, l’uso corretto dei dispositivi di protezione individuale (DPI) e l’attenzione ai rischi e alle misure di protezione specifiche per ogni procedura otorinolaringoiatrica sono della massima importanza. In conclusione, questa review evidenzia che l’attività otorinolaringoiatrica implica un alto rischio di contagio in occasione di visite, interventi chirurgici o trattamento di condizioni urgenti. Il corretto utilizzo dei DPI, la valutazione dei rischi specifici di ogni procedura e la riduzione di visite e interventi non urgenti sono considerate le principali strategie per limitare il contagio.
... Coronaviruses (CoVs) are part of the Orthocoronavirinae subfamily of the Coronaviridae family of the Order Nidovirales. The Orthocoronavirinae subfamily is subdivided into four genera those includes Alphacoronavirus (-CoV), Betacoronavirus (-CoV), Gammacoronavirus (-CoV), and Deltacoronavirus (-CoV) 3,4 . The World Health Organization reports that the outbreak of the deadly virus had been noted almost in all the countries worldwide. ...
Background: The World Health Organization (WHO) reports that the outbreak of the deadly virus had been noted almost in all the countries worldwide. Newly no standard therapies are available to combat the situation and this remains the major challenge for healthcare professionals to provide effective treatment against the life-threatening condition. A potential regenerative medicine method using the infusion of stem cells for the treatment of lung disorders has been reported. This review attempted to explore the immunomodulatory characteristics of Mesenchymal Stem Cells (MSCs) and how these properties make them beneficial for the treatment of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) patients. Objectives: To study the effect of Mesenchymal Stem Cell therapy in treating COVID-19. Methodology: A literature search was conducted to identify recent research relating to the review's goal of analyzing the relevance of stem cells in battling SARS-CoV-2. Results: The MSCs settle in the lungs intravenously to enhance the pulmonary microenvironment, minimize immune system over-activation, and encourage regeneration of damaged lung tissues. Its therapeutic properties like immune response inhibition play a major role in combating viruses. The avoidance of cytokine storm is the most important stage in COVID-19 therapy. Their potent immunomodulatory properties have positive effects in avoiding or attenuating the cytokine storm and assisting in the regeneration of injured lung tissues/other organs. Conclusion: Intravenous human Umbilical Cord-Mesenchymal Stem Cell therapy (hUC-MSC) transplantation is a safe and effective technique that may be used as a restoration and prioritized therapeutic option for treating severe COVID-19. Keywords: Covid-19, human Umbilical Cord-Mesenchymal Stem Cell therapy (huc-msc), Immune system.
... In the current article we focus on the immunological mechanisms of natural resistance to pathogens. A strong argument for the relevance of immunological mechanisms to natural resistance to pathogens is given by the type of immune response elicited against an infection in humans versus other species: for example, bats, unlike humans, respond to coronavirus infection with high production of interferons (IFNs) and low inflammation, which is a likely mechanism that induces a high level of tolerance against such infections [1] (Box 1). By contrast, humans are known to respond with a strong inflammatory reaction during many viral infections such as those caused by influenza virus or coronaviruses [2,3]. ...
Not all individuals exposed to a pathogen will develop illness: some are naturally resistant; others will develop an asymptomatic infection. Epidemiological studies suggest that similar variability in susceptibility exists against SARS-CoV-2 infections. We propose that natural resistance is part of disease history in some individuals exposed to this new coronavirus. Epidemiological arguments for natural resistance to SARS-CoV-2 are the lower seropositivity of children compared to adults, studies on closed environments of ships with outbreaks, and prevalence studies in some developing countries. Potential mechanisms of natural resistance include host genetic variants, viral interference, cross-protective natural antibodies, T-cell immunity, and highly effective innate immune responses. A better understanding of natural resistance can help advance preventive and therapeutic measures against infections for improved preparedness against potential future pandemics.
... They belong to the subfamily Orthocoronavirinae within the family Coronaviridae. The four genera within this subfamily include Alphacoronavirus, Betacoronavirus, Deltacoronavirus, and Gammacoronavirus (Yang and Leibowitz 2015;Banerjee et al. 2019). The αand βcoronaviruses have great medical and veterinary significance and contain 17 and 12 species, respectively. ...
The novel β-coronavirus, SARS-CoV-2, responsible for the coronavirus disease 2019 (COVID-19) emerged in China in December 2019. Due to its high transmission and infection rate, it has spread around the world and has transformed into a ravaging global pandemic with enormously unprecedented impacts globally on human, social, and economic health. Just like SARS-CoV and MERS-CoV, there is no specific antiviral drug for its treatment. The only available therapeutics are supportive and symptom-based. Thus, scientists are harnessing various strategies to expedite drug development. One such approach is drug repurposing through computational screening of phytocompounds, which leverages proteins that are essential for the entry, replication, pathogenesis, assembly, and release of SARS-CoV-2. Here, we review the available literature on molecular docking of phytoligands against SARS-CoV-2 integral proteins, in a bid to update our current knowledge and identify the most promising molecules. The overwhelming majority of the promising lead compounds are either phenolics or terpenoids. Furthermore, of the elucidated SARS-CoV-2 targets, the main protease (3CLpro) appears as one of the most attractive druggable targets. Notably, compounds such as rutin, quercetin, luteolin, neoandrographolide, curcumin, and others with evident anti-inflammatory benefits, in addition to their predicted anti-SARS-CoV-2 properties, deserve further studies to validate their activity.
... However, researchers have not determined which animal is responsible for the final transmission to humans. Bats are the natural hosts for some of the most dangerous viruses, including Ebola, Marburg, rabies, Hendra, and Nipah [15]. Due to their special immunological features, bats are naturally infected but do not exhibit clinical signs of these diseases [16]. ...
Since the end of 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. The RNA genome of SARS-CoV-2, which is highly infectious and prone to rapid mutation, encodes both structural and nonstructural proteins. Vaccination is currently the only effective method to prevent COVID-19, and structural proteins are critical targets for vaccine development. Currently, many vaccines are in clinical trials or are already on the market. This review highlights ongoing advances in the design of prophylactic or therapeutic vaccines against COVID-19, including viral vector vaccines, DNA vaccines, RNA vaccines, live-attenuated vaccines, inactivated virus vaccines, recombinant protein vaccines and bionic nanoparticle vaccines. In addition to traditional inactivated virus vaccines, some novel vaccines based on viral vectors, nanoscience and synthetic biology also play important roles in combating COVID-19. However, many challenges persist in ongoing clinical trials.
... Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible infection, first identified in December 2019, Wuhan city, Hubei Province, in China [1,2]. The causative agent of this serious illness is termed positive-sense single-stranded ribonucleic acid [6] and can be classified into four genera: alpha coronaviruses, beta coronaviruses, gamma coronaviruses, and delta coronaviruses [7][8][9]. ...
Background and Aims: The current preliminary study aimed to assess the clinical symptoms of the 67 Iranian COVID-19 patients and investigate the possible beneficial effects of the naproxen compared to the standard therapeutic regimen. Materials and Methods: We assessed 67 COVID-19 patients. All COVID-19 cases were confirmed by computed tomography (CT) and real time-polymerase chain reaction tests. We evaluated the clinical symptoms of the patients at the admission time. Also, a group of 28 patients received naproxen besides their standard treatment. Clinical presentations, radiographic features, white blood cells (WBC) in peripheral blood, hemoglobin, platelets, C-reactive protein, erythrocyte sedimentation rate, blood urea nitrogen, lactate dehydrogenase, Albumin, and Creatine Phosphokinase were evaluated. Results: The patients' clinical symptoms show that cough (89.6%) was the most repeated signed at the admission time, followed by fever at 78.7%, fatigue at 70%, and myalgia at least 64.2%. Unilateral slight ground-glass opacity was the most abundant presentation by 64.1% in CT. The laboratory assessment in patients indicates that mean WBC was 6193 ± 3258 (x106/L), and mean lymphocyte was 27.8 ± 12%. The survival rate and the hospitalization days for patients with or without the Naproxen regimen were not statistically significant. Conclusion: The most common clinical symptoms in Iranian patients with COVID-19 at the admission time include cough, fever, fatigue, and myalgia. Based on the current study results, the survival rate and the hospitalization days for patients with or without Naproxen usage were not statistically significant. The laboratory parameters could not show any particular statistically significant differences.
... Emerging zoonotic viruses require a natural wildlife reservoir host; these host species are essential for the maintenance of viruses in the environment but natural wildlife reservoir hosts present no evidence of infection. Bats have been suspected to be potential natural reservoirs of various viruses of concern for public health (Calisher et al. 2006;Allocati et al. 2016), such as filoviruses (Ebola and Marburg that cause hemorrhagic fevers; Peterson et al. 2004;Leroy et al. 2005Leroy et al. , 2009Leendertz et al. 2015) and certain types of coronaviruses closely related to the coronaviruses responsible for acute respiratory syndromes such as MERS (Middle East Respiratory Ayndrome), SARS (Severe Acute Respiratory Syndrome) (Banerjee et al. 2019), and the novel SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) (Zhang et al. 2020). The assertion that bats have served as the natural reservoir for these pathogens is due to the fact that closely related variants of these viruses have been found in some bat species, with hosts demonstrating high viral tolerance (Calisher et al. 2006;Negredo et al. 2011;Allocati et al. 2016;Letko et al. 2020;Zhou et al. 2020). ...
The Order Chiroptera comprises more than 1,400 species, each with its evolutionary history and under unique selective pressures, among which are the host–pathogen interactions. Bats have coped with complex interactions with a broad spectrum of microbes throughout their evolutionary history, prompting the development of unique adaptations that allow them to co-exist with microbes with pathogenic potential more efficiently than other nonadapted species. In this sense, an extraordinary immune system with unique adaptations has been hypothesized in bats. To explore this, we focused on the major histocompatibility complex (MHC), which plays a crucial role in pathogen recognition and presentation to T cells to trigger the adaptive immune response. We analyzed MHC class I transcripts in five species, each from different families of New World bats. From RNA-seq data, we assembled a partial region of the MHC-I comprising the α1 and α2 domains, which are responsible for peptide binding and recognition. We described five putative functional variants, two of which have two independent insertions at the α2 domain. Our results suggest that this insertion appeared after the divergence of the order Chiroptera and may have an adaptive function in the defense against intracellular pathogens, providing evidence of positive selection and trans-specific polymorphism on the peptide-binding sites.
... Coronaviruses are a group of viruses with a wide range of phenotypic and genotypic diversity; the rapid and steady spread of Coronavirus 2019 (COVID 19) has put many people's health and lives at risk and has posed several concerns for health systems in different countries. According to the literature, the four forms of coronas are Alpha, Beta, Gamma, and Delta (1). Coronaviruses have historically been associated with human infections followed by enzyme infections in birds and rodents (2). ...
The COVID-19 pandemic has caused many of us to stay constantly hospitalized and isolated. In addition, this has severe long-term mental health impacts such as depression, post-traumatic stress, anxiety, rage, anger, and opioid addiction. Consequently, it leads to the growth of Sedentary Death Syndrome and impairs the cognitive ability of individuals. Even so, it was shown to be necessary to support an individual's condition and general wellbeing when a person leads a physically active lifestyle or is involved in regular home exercise. Regular strength exercise in the home, provides a variety of effects Which has a direct positive effect on a person's mental health. as the WHO has recently mandated, the accumulation of at least sixty minutes of moderate-to-intensity physical activity every day for children aged 6 to 17, as well as on two days per week for adults in order to increase bone and muscular strength, there is a very strong correlation between getting enough exercise and becoming healthy.
... SARS-CoV-2, like other CoVs, is an RNA virus that is a member of the subfamily Orthocoronavirinae, the order Nidovirales, and the genus coronavirus. Coronaviruses are enclosed and have positive sense singlestranded RNA genomes ranging in size from 26 to 32 kb [3]. The electron microscopic appearance of the SARS-CoV-2 particle resembled that of a solar corona, with a diameter of 60 to 140 nm and spikes measuring approximately 9 to 12 nm. ...
Few peculiarities have been observed in the aetiology of coronavirus disease 2019 (COVID-19), one such being its greater prevalence in men than women partly due to the higher expressions of angiotensin-converting enzyme-2 (ACE2) in the male reproductive tissues. Recent scientific reports are in line with some of the evidence-based hypotheses in the initial phase of the COVID-19 pandemic, regarding the involvement of oxidative stress (OS) and oxidant-sensitive pathways in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-mediated male reproductive disruptions. The seminal dissemination of SARS-CoV-2 or its components, testicular disruptions due to viral infection and oxidative damage in the testis have all been evidenced recently. High-dose of antioxidants, such as vitamin C, have been shown to be a useful treatment for COVID-19 patients, to alleviate systemic inflammation and OS. In addition, vitamin C is a major testicular antioxidant that neutralizes excess reactive oxygen species (ROS), prevents sperm agglutination, prevents lipid peroxidation, recycles vitamin E, and protects against DNA damage. Thus, the present review aims to discuss the mechanism of COVID-19-mediated male reproductive dysfunctions, based on the evidence available so far, and explore the possibility of using vitamin C in alleviating testicular OS and associated damage caused by COVID-19.
... The infected individuals may also show hepatic, respiratory, neurological, and gastrointestinal complications that can eventually lead to death. [5][6][7][8] Elderly patients and those who required intensive care support mostly had multiple comorbidities, including cardiovascular, cerebrovascular, endocrine, digestive, and respiratory diseases. 5,9) Though young and healthy people do not fall under major risk groups, they could act as carriers affecting the higherrisk groups. ...
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-COV-2), has rapidly spread worldwide, causing many deaths, the number of which continues to increase. Global public health organizations and governments have advised on the adoption of various handwashing and hygiene guidelines, use of masks, and social distancing, along with isolation or lockdown protocols to prevent SARS-COV-2 spread. There are vaccines and drugs that are confirmed but still many human suffer from this disease. Important risk factors for SARS-COV-2 infection are similar to other viral infectious diseases as including influenza, hepatitis B, acquired immunodeficiency syndrome, and other lung infections. These diseases might be related to poor nutritional support, affecting the patient outcomes against COVID-19. In this review, we discuss some of the nutritional therapies currently being investigated for infectious diseases. Studies have shown that nutrition has the potential to prevent and mitigate viral infections. Micronutrients (vitamins A, B6, B12, C, D, and E, B9, and trace elements, such as iron, zinc, copper, selenium, magnesium, and polyphenols) and macronutrients (carbohydrates, prebiotics, probiotics, protein [amino acids], and lipids [fatty acids]) affect the whole body, including the immune system, preventing viral entry and modulating clinical symptoms. This review discusses the importance of nutrition as a strategy to understand food groups and key nutrients that may affect the clinical outcomes of COVID-19 patients during the ongoing pandemic. Scientists believe that the likelihood of another pandemic is imminent. COVID-19 remains important and scientists believe it will continue will in the future. We emphasize the lack of studies on the nutritional impact of COVID-19 in terms of nutrition, even though nutritional interventions has been shown to have many advantages during the treatment of viral infections.
... Indeed, the wild animal reservoirs of SARS-1, SARS-CoV-2, and Middle East respiratory syndrome (MERS)-CoV are still not known. Indeed, while there is good evidence that dromedaries and bats may harbor MERS-CoV (24,25), and horseshoe bats harbor SARS (26), wild animal reservoirs of SARS, SARS-CoV-2, and MERS-CoV are still not well understood. There have been numerous cases of isolated human-to-animal transmission of SARS-CoV-2 involving companion, farmed, and zoo animals since the COVID-19 pandemic began (8,9,27,28). ...
Many animal species are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and could act as reservoirs; however, transmission in free-living animals has not been documented. White-tailed deer, the predominant cervid in North America, are susceptible to SARS-CoV-2 infection, and experimentally infected fawns can transmit the virus. To test the hypothesis that SARS-CoV-2 is circulating in deer, 283 retropharyngeal lymph node (RPLN) samples collected from 151 free-living and 132 captive deer in Iowa from April 2020 through January of 2021 were assayed for the presence of SARS-CoV-2 RNA. Ninety-four of the 283 (33.2%) deer samples were positive for SARS-CoV-2 RNA as assessed by RT-PCR. Notably, following the November 2020 peak of human cases in Iowa, and coinciding with the onset of winter and the peak deer hunting season, SARS-CoV-2 RNA was detected in 80 of 97 (82.5%) RPLN samples collected over a 7-wk period. Whole genome sequencing of all 94 positive RPLN samples identified 12 SARS-CoV-2 lineages, with B.1.2 ( n = 51; 54.5%) and B.1.311 ( n = 19; 20%) accounting for ∼75% of all samples. The geographic distribution and nesting of clusters of deer and human lineages strongly suggest multiple human-to-deer transmission events followed by subsequent deer-to-deer spread. These discoveries have important implications for the long-term persistence of the SARS-CoV-2 pandemic. Our findings highlight an urgent need for a robust and proactive “One Health” approach to obtain enhanced understanding of the ecology, molecular evolution, and dissemination of SARS-CoV-2.
... Phylogenetically, coronaviruses are classified in the subfamily Orthocoronavirinae, of the family Coronaviridae, order Nidovirales (Banerjee et al., 2019). Coronaviruses are divided into four genera: Alphacoronavirus (α-CoV) and Betacoronavirus (β-CoV), which primarily infect J o u r n a l P r e -p r o o f mammals as their hosts, and Gammacoronavirus (γ-CoV) and Deltacoronavirus (δ-CoV), which mainly infect birds (Woo et al., 2014;Schütze, 2016;Bossart and Duignan, 2018). ...
In 2019, the world faced a serious health challenge, the rapid spreading of a life-threatening viral pneumonia, coronavirus disease 2019 (COVID-19) caused by a betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of January 2022 WHO statistics shows more than 5.6 million death and about 350 million infection by SARS-CoV-2. One of the life threatening aspects of COVID-19 is secondary infections and reduced efficacy of antibiotics against them. Since the beginning of COVID-19 many researches have been done on identification, treatment, and vaccine development. Bacterial viruses (bacteriophages) could offer novel approaches to detect, treat and control COVID-19. Phage therapy and in particular using phage cocktails can be used to control or eliminate the bacterial pathogen as an alternative or complementary therapeutic agent. At the same time, phage interaction with the host immune system can regulate the inflammatory response. In addition, phage display and engineered synthetic phages can be utilized to develop new vaccines and antibodies, stimulate the immune system, and elicit a rapid and well-appropriate defense response. The emergence of SARS-CoV-2 new variants like delta and omicron has proved the urgent need for precise, efficient and novel approaches for vaccine development and virus detection techniques in which bacteriophages may be one of the plausible solutions. Therefore, phages with similar morphology and/or genetic content to that of coronaviruses can be used for ecological and epidemiological modeling of SARS-CoV-2 behavior and future generations of coronavirus, and in general new viral pathogens. This article is a comprehensive review/perspective of potential applications of bacteriophages in the fight against the present pandemic and the post-COVID era.
... The novel coronaviruses 2019 (nCoV-2019 or COVID- 19) cannot be talked about in isolation of bats who serve as reservoir host [1] and are present in urban settlements [2,3]. The which is caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARs-CoV-2) had been declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) on 30 th January 2020 and was subsequently declared a global pandemic by the WHO on 11 th March 2020 [4,5]. ...
Dreaded realities await us each day as we wake up due to the impact of anthropogenic
activities. Coronavirus disease 2019 (COVID-19) has etched itself into every aspect of our
lives, changing the way we behave and creating new normal. Our consumption habit has
been unsustainable even before coronavirus hit. COVID-19 has just made a bad situation
much worse. Since news of the coronavirus was first announced in January, its horrors
have not stopped. The number of cases worldwide is still rising, and its death toll is
appallingly high. Lockdowns was introduced in order to curb transmission of COVID-19
in which both e-commerce and health sectors resolved to using plastics (‘known
unknowns’). There is no denying that single-use plastic has been a lifesaver in the fight
against COVID-19, especially for frontline health workers. It has also facilitated adherence
to social-distancing rules, by enabling home delivery of basic goods, especially food. And
it may have helped to curb transmission, by replacing reusable coffee cups and shopping
bags in many cities over fears that the virus could stick to them. Though other studies
have shown that SARS-COV-2 still last longer on single-use plastics (72 hours) than
on cardboard (24 hours) and yet the paper industry association is not using this as an
opportunity to lobby or directly profit from the crisis in comparison to the plastic industry
association appealing for reversal on the ban of single-use plastics. Plastic pollution
impacts behind the scenes on public and environmental health have both short- and long-
term effects. Plastic-to-Ocean movement has created a lot of micro-and nano plastics in
an alarming rate. The question is, would the COVID-19 crisis prompt innovation for waste
reduction, as it had for virtual health access, small business e-commerce, community
collaboration and more? This review suggests recent environmentally friendly and
sustainable plastic waste management practices. Plastic waste would be a thing of the
past through the most recent molecular re-engineering technique which combined two
super enzymes, PETase and MHETase which yielded a faster breakdown of PET. Also,
plastic waste can be fought through the use of underwater robot called Smart Infrared
Based Remotely Operated Vehicle to identify microplastics in marine environments. The way forward towards a near-zero plastic waste in the ongoing-and post-COVID-19 era
demands that we let go business-as-usual and simultaneously adopt the System Change
Scenario concept. If returning back to normal is not an option, perhaps the best hope we
can find in our present situation is this: there is no better time for change than now. The
COVID-19 pandemic is an eye opener towards a need for cooperation among individuals,
expert organizations, and the government for a more sustainable environment.
... Historically it was believed, that coronavirus was causing respiratory and enteric illness only in farm animals, but the emerging coronaviruses (beta-coronavirus) are proved to be pathogenic to humans as well, causing severe respiratory and gastrointestinal symptoms [3]. Unlike the previous pathogenic CoVs, the global pandemic causing SARS-CoV2 has a range of 0.2-9% with an average of 2% case fatality ratio, which also varied in different countries, but the highly contagious nature of the virus had made it the most consequential global health crisis. ...
COVID-19 pandemic has emerged as a global threat with its highly contagious and mutating nature. Several existing antiviral drugs has been worked on, without proper results and meanwhile the virus is mutating rapidly to create more infectious variant. In order to find some alternatives, phytocompounds can be opted as good one. In this study, three hundred phytocompounds were screened virtually against two viral proteins namely main protease and spike protein. Molecular docking and dynamic simulation study was used to find binding affinity, structural stability and flexibility of the complex. Pharmacokinetic properties were studied through ADMET analysis. To understand energy variation of the complex structure free energy landscape analysis was performed. Among three hundred phytocompounds virtual screening, three phytocompounds were selected for detailed molecular interaction analysis. Oleanderolide, Proceragenin A and Balsaminone A, showed strong binding affinity against both the target proteins and reflected conformational stability throughout the MD run. Oleanderolide, proceragenin A and balsaminone A has docking score −9.4 kcal/mol, −8.6 kcal/mol, and −8.1 kcal/mol respectively against main protease and same −8.3 kcal/mol docking score against spike protein. These three phytocompounds has high gastrointestinal absorption capacity. They were unexplored till now for their antiviral activity. Their promising in silico results suggests that they can be promoted in the long run for development of new antiviral drugs.
... Historically it was believed, that coronavirus was causing respiratory and enteric illness only in farm animals, but the emerging coronaviruses (beta-coronavirus) are proved to be pathogenic to humans as well, causing severe respiratory and gastrointestinal symptoms [3]. Unlike the previous pathogenic CoVs, the global pandemic causing SARS-CoV2 has a range of 0.2-9% with an average of 2% case fatality ratio, which also varied in different countries, but the highly contagious nature of the virus had made it the most consequential global health crisis. ...
... Coronaviruses are belonging to the Coronaviridae family with the subfamily of Orthocoronavirinae in the order of Nidovirales [9] (Figure 1). Coronavirinae is further divided into four genera: alpha, beta, gamma, and delta coronavirus [10]. ...
Presently, an outbreak of coronavirus is of global concern, as it causes various respiratory problems. It was first detected in December 2019 in China’s Wuhan City where various patients got admitted to the hospitals with a symptom of pneumonia. As the number of cases increased, scientists isolated the samples from patients. Initially, it was named as a novel coronavirus (2019-nCoV) and now renamed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus spread from Wuhan to other cities of China, and currently it is affecting worldwide. Transmission of this virus occurs from one human to another and spreads through contaminated hands or surfaces. Various researchers are trying to explore the potential role of bioactive compounds from plants and different nanomaterials against this virus. Therefore, in this review, an overview of SARS-CoV-2, preventive measures against this viral infection, potential biocides against this virus, and role of phytochemicals and nanomaterials against this virus have been discussed.
... In the case of bats, it is largely unknown to what extent the immune system influences the manifestation of viral diseases or their progression. However, recent research suggests that bats have evolved unique features to fight RNA viruses [75]. One of the most important findings is the discovery of an attenuated inflammatory response in bats [33,76] that is tightly connected to the IFN response. ...
Eidolon helvum bats are reservoir hosts for highly pathogenic lyssaviruses often showing limited disease upon natural infection. An enhanced antiviral interferon (IFN) response combined with reduced inflammation might be linked to the apparent virus tolerance in bats. Lyssavirus phosphoproteins inhibit the IFN response with virus strain-specific efficiency. To date, little is known regarding the lyssavirus P-dependent anti-IFN countermeasures in bats, mainly due to a lack of in vitro tools. By using E . helvum bat cell cultures in a newly established bat-specific IFN-promoter activation assay, we analyzed the IFN-ß inhibitory activity of multiple lyssavirus P in E . helvum compared to human cells. Initial virus infection studies with a recently isolated E . helvum -borne Lagos bat virus street strain from Ghana showed enhanced LBV propagation in an E . helvum lung cell line compared to human A549 lung cells at later time points suggesting effective viral countermeasures against cellular defense mechanisms. A direct comparison of the IFN-ß inhibitory activity of the LBV-GH P protein with other lyssavirus P proteins showed that LBV-GH P and RVP both strongly inhibited the bat IFN-β promotor activation (range 75–90%) in EidLu/20.2 and an E . helvum kidney cell line. Conversely, LBV-GH P blocked the activation of the human IFN-β promoter less efficiently compared to a prototypic Rabies virus P protein (range LBV P 52–68% vs RVP 71–95%) in two different human cell lines (HEK-293T, A549). The same pattern was seen for two prototypic LBV P variants suggesting an overall reduced LBV P IFN-ß inhibitory activity in human cells as compared to E . helvum bat cells. Increased IFN-ß inhibition by lyssavirus P in reservoir host cells might be a result of host-specific adaptation processes towards an enhanced IFN response in bat cells.
... Despite the clear insights afforded by experiments, model bat systems are heavily limited by logistical constraints (e.g., necessity for specialized facilities, colony maintenance) and have been mostly focused on frugivorous bats, which are relatively easy to keep in captivity compared to other dietary guilds (34,35). Transcriptomics of key tissues (e.g., spleen) has helped advance the field by identifying immune responses to infection in a wider array of species (36)(37)(38). ...
The apparent ability of bats to harbor many virulent viruses without showing disease is likely driven by distinct immune responses that coevolved with mammalian flight and the exceptional longevity of this order. Yet our understanding of the immune mechanisms of viral tolerance is restricted to a small number of bat–virus relationships and remains poor for coronaviruses (CoVs), despite their relevance to human health. Proteomics holds particular promise for illuminating the immune factors involved in bat responses to infection, because it can accommodate especially low sample volumes (e.g., sera) and thus can be applied to both large and small bat species as well as in longitudinal studies where lethal sampling is necessarily limited. Further, as the serum proteome includes proteins secreted from not only blood cells but also proximal organs, it provides a more general characterization of immune proteins. Here, we expand our recent work on the serum proteome of wild vampire bats (Desmodus rotundus) to better understand CoV pathogenesis. Across 19 bats sampled in 2019 in northern Belize with available sera, we detected CoVs in oral or rectal swabs from four individuals (21.1% positivity). Phylogenetic analyses identified all RdRp gene sequences in vampire bats as novel α-CoVs most closely related to known human CoVs. Across 586 identified serum proteins, we found no strong differences in protein composition nor abundance between uninfected and infected bats. However, receiver operating characteristic curve analyses identified seven to 32 candidate biomarkers of CoV infection, including AHSG, C4A, F12, GPI, DSG2, GSTO1, and RNH1. Enrichment analyses using these protein classifiers identified downregulation of complement, regulation of proteolysis, immune effector processes, and humoral immunity in CoV-infected bats alongside upregulation of neutrophil immunity, overall granulocyte activation, myeloid cell responses, and glutathione processes. Such results denote a mostly cellular immune response of vampire bats to CoV infection and identify putative biomarkers that could provide new insights into CoV pathogenesis in wild and experimental populations. More broadly, applying a similar proteomic approach across diverse bat species and to distinct life history stages in target species could improve our understanding of the immune mechanisms by which wild bats tolerate viruses.
These days, the extreme intense respiratory condition Coronavirus 2 (SARS-CoV-2) disease is recognized on the grounds that the primary cause behind mortality in people. SARS-CoV-2 is transmitted through human-to-human contact and is a symptomless in many patients. furthermore, to approved vaccines against SARS-CoV-2 infection, miRNAs may additionally be promising decisions against the current new virus. miRNAs are small and noncoding RNAs 18–25 nucleotides in length that focus on the mRNAs to degrade them or block their interpretation miRNAs go about as an observer in cells.
This review in regards to evaluated the writing on the potential role of cellular miRNAs inside the SARS-CoV-2-have collaboration as a therapeutic option in COVID-19 patients.
In December 2019, a new form of coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started spreading in Wuhan, China. According to the situation report-95 published by the World Health Organization (WHO), the coronavirus disease spread rapidly to 213 countries and territories by April 24, 2020, with the number of confirmed cases and deaths of 26,26,321 and 1,81,938, respectively. The WHO declared coronavirus disease 2019 (COVID-19) as a pandemic on March 11, 2020. People living in many countries are in lockdown and staying at home because of this deadly virus. Patients of COVID-19 are reported to have single or multiple symptoms, while some patients do not have any remarkable symptom at all. Patients have reported symptoms of dry cough, sore throat, fever, fatigue, breathing problem, and gastrointestinal infection. COVID-19 may become very dangerous especially for aged people and people with any other disease such as diabetes, kidney problem, etc. In that case, the virus can cause acute respiratory distress syndrome and cytokine storm. The whole world is in lockdown because of this deadly virus. Currently, there is no particular cure for this disease; however, researchers are trying to find appropriate antiviral and repurposed drugs. This chapter provides a review on the different aspects of COVID-19 including the epidemiology, genomic sequence, and clinical characteristics; current medical treatment options; and development of vaccines and drugs.
The spread of coronavirus disease 2019 (COVID-19) in various countries varies in different manners, depending on the demographic and climatic conditions. This needs expediting better strategies to combat the novel coronavirus and also the emergence of new viral strains in the future. Our in-depth analysis suggests the spread of COVID-19 cases worldwide, the timeline of spread among most affected countries as of September 3, 2020. Evaluation of the climatic conditions in 2-week interval is carried out. The study recorded most of the countries getting affected by COVID-19 belong to the range of 25–35°C maximum temperature, 20–30°C minimum temperature, and 60%–80% relative humidity. To get a more generalized view on the spread, the study explored the temperature distribution of affected countries and chronicled in both minimum and maximum temperatures so that the number of COVID-19 cases mostly follows a lognormal distribution. In different ranges of relative humidity, not a single distribution is obtained to explain the spread of COVID-19 cases worldwide. A comparison between theoretic and descriptive parameters is also done to support the spread of COVID-19.
Ecological and experimental infection studies have identified Egyptian rousette bats (ERBs; Rousettus aegyptiacus: family Pteropodidae) as a reservoir host for the zoonotic rubula-like paramyxovirus Sosuga virus (SOSV). A serial sacrifice study of colony-bred ERBs inoculated with wild-type, recombinant SOSV identified small intestines and salivary gland as major sites of viral replication. In the current study, archived formalin-fixed paraffin-embedded (FFPE) tissues from the serial sacrifice study were analyzed in depth—histologically and immunohistochemically, for SOSV, mononuclear phagocytes and T cells. Histopathologic lesion scores increased over time and viral antigen persisted in a subset of tissues, indicating ongoing host responses and underscoring the possibility of chronic infection. Despite the presence of SOSV NP antigen and villus ulcerations in the small intestines, there were only mild increases in mononuclear phagocytes and T cells, a host response aligned with disease tolerance. In contrast, there was a statistically significant, robust and targeted mononuclear phagocyte cell responses in the salivary glands at 21 DPI, where viral antigen was sparse. These findings may have broader implications for chiropteran–paramyxovirus interactions, as bats are hypothesized to be the ancestral hosts of this diverse virus family and for ERB immunology in general, as this species is also the reservoir host for the marburgviruses Marburg virus (MARV) and Ravn virus (RAVV) (family Filoviridae).
The disease coronavirus disease 2019 (COVID-19) is a severe respiratory illness that has emerged as a devastating health problem worldwide. The disease outcome is heterogeneous, and severity is likely dependent on the immunity of infected individuals and comorbidities. Although symptoms of the disease are primarily associated with respiratory problems, additional infection or failure of other vital organs are being reported. Emerging reports suggest a quite common co-existence of gastrointestinal (GI) tract symptoms in addition to respiratory symptoms in many COVID-19 patients, and some patients show just the GI symptoms. The possible cause of the GI symptoms could be due to direct infection of the epithelial cells of the gut, which is supported by the fact that (1) The intestinal epithelium expresses a high level of angiotensin-converting enzyme-2 and transmembrane protease serine 2 protein that are required for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into the cells; (2) About half of the severe COVID-19 patients show viral RNA in their feces and various parts of the GI tract; and (3) SARS-CoV-2 can directly infect gut epithelial cells in vitro (gut epithelial cells and organoids) and in vivo (rhesus monkey). The GI tract seems to be a site of active innate and adaptive immune responses to SARS-CoV-2 as clinically, stool samples of COVID-19 patients possess proinflammatory cytokines (interleukin 8), calprotectin (neutrophils activity), and immunoglobulin A antibodies. In addition to direct immune activation by the virus, impairment of GI epithelium integrity can evoke immune response under the influence of systemic cytokines, hypoxia, and changes in gut microbiota (dysbiosis) due to infection of the respiratory system, which is confirmed by the observation that not all of the GI symptomatic patients are viral RNA positive. This review comprehensively summarizes the possible GI immunomodulation by SARS-CoV-2 that could lead to GI symptoms, their association with disease severity, and potential therapeutic interventions.
Severe acute respiratory syndrome-CoV-2 was declared as a pandemic by the World Health Organization in March 2020. The virus belongs to the family Coronaviridae and causes infection of varying severity ranging from mild respiratory tract infection to severe pneumonia or acute respiratory disease syndrome. Several laboratory parameters are deranged in COVID-19 infection. The gold standard of diagnosis of COVID-19 infection is polymerase chain reaction (PCR) from the nasopharyngeal and oropharyngeal swab. However, at remote places, where PCR reports are made available to patients after a time gap laboratory parameters may guide the treating physician regarding diagnosis, disease severity, and prognosis.
What can you do to improve your health and at the same time improve the health of our home planet? Do you want to be a healthier and more sustainable consumer? In this straightforward, easy-to-understand and entertaining book, dietitian and environmentalist Dr. Dana Ellis Hunnes outlines the actions we can all take. Many people feel overwhelmed by the scope of climate change and believe that only large, sweeping changes will make any difference. Yet the choices we make every day can have effects on climate change, the oceans, the land, and other species. This book outlines the problems we are facing, and then presents ideas or 'recipes' to empower us, to help us all make a difference. Recipe For Survival provides the guidance that you can use right now to improve your health, your family's health, and the health of the environment simultaneously.
The ongoing coronavirus disease 2019 (COVID-19) pandemic is having devastating impacts across the globe. Among the implemented policies to reduce the spread of the disease is lockdown. This might have serious impact on farming activities and the livelihoods of millions of people whose daily means of sustenance is tied to agricultural activities. We undertook this study in West Africa, one of the most fragile and vulnerable regions to the epidemic. Our aim was to understand (1) farmers' perception of the impact of COVID-19 and lockdown policies on their farm or business revenue, (2) farmers' preparedness for COVID-19 lockdown on their farm or business revenue, and (3) the impact of effectiveness of COVID-19 lockdown on their farm or business revenue. We combined online questionnaire, physical contact and administration, and social media (Facebook and WhatsApp) to get responses from 303 farmers in Nigeria and Ghana. Our findings show that COVID-19 and lockdown policies negatively affected the farmers. The impact of COVID-19 and lockdown policies on respondents' farm or business revenue was independent of either age or gender of respondents and the effectiveness of lockdown in both the countries. The status of lockdown in respondent places (locked down versus not locked down) and the level of preparedness of farmers to handle the situation with the current COVID-19 crisis in their farms were also independent in both the countries. However, we found that the impact of COVID-19 and lockdown policies on farm or business revenue depends on the level of preparedness of farmers to handle the situation in each country. We further found that the impact of COVID-19 and lockdown policies on farm or business revenue was independent of the status of lockdown but rather depended on the preparedness for the current COVID-19 crisis and differently across countries. Our findings suggest that building capacities of farmers and supporting them in preparedness for such occurrence, as well as establishing and implementing public policies in this direction, can mitigate the impact of the pandemic on their activities.
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.
The prevalence of coronavirus disease 2019 (COVID-19) exacerbated investor fears, uncertainties, and increased volatility in financial markets. The reaction to oil prices gradually absorbed the epidemic until March 08, but the market situation changed soon with a sharp drop in prices until April 17. This study aims to verify the impact of COVID-19 cases on crude oil prices and the Saudi economy. A simple linear regression estimate shows that new daily outbreaks have a marginally negative impact on crude oil prices in the short term. However, COVID-19 also has an indirect effect on the recent volatility in crude oil prices.
Solutions include proactive management, and we emphasize that special consideration must be given to the size of the supply to properly forecast oil prices. Volatility dominates in the short term. The relationship between the epidemic and oil prices reveals a root cause. Moreover, we investigate the interaction between the epidemic and oil prices, with the effective implementation of these solutions with the government's full support.
Background:
High alcohol consumption is an important public health problem, and understanding factors associated with such consumption is essential.
Aims:
This study aimed to assess individual and social factors associated with alcohol consumption during the coronavirus disease 2019 (COVID-19) pandemic in the Islamic Republic of Iran.
Methods:
In this qualitative study, purposive sampling was used to select study participants by sharing the survey link on the Telegram application channels with an Iranian audience during COVID-19. The study was conducted from March to June 2020 and reached all Iranian provinces. We used qualitative content analysis to investigate specific concepts in the responses.
Results:
Of the 116 participants who responded to the survey, 34 (29.3%) were females, and 82 (70.7%) were male. The mean age of the participants was 34.8 years (standard deviation 9.9; range 17-71 years). Most of the participants (75.9%) reported having consumed alcohol, and 56.9% reported having self-medicated for an illness without a doctor's prescription before the COVID-19 pandemic. The most common reason given for alcohol consumption was to relieve stress during home quarantining (32.3%). Based on analysis of the responses, two themes emerged: coping motivations and coping skills, with five subthemes and 14 basic codes. Coping motivations were more powerful than coping skills in relation to high alcohol consumption.
Conclusion:
Poor coping skills and strong motivations, combined with misinformation on social media and the internet, appear to have led to new or higher alcohol consumption among survey respondents.
As SARS-CoV-2 emerge, variants such as Omicron (B.1.1.529), Delta (B.1.617.2), and those from the United Kingdom (B.1.1.7), South Africa (B.1.351), Brazil (P.1) and India (B.1.6.17 lineage) have raised concerns of the reduced neutralising ability of antibodies and increased ability to evade the current six approved COVID-19 vaccine candidates. This viewpoint advocates for countries to conduct prior efficacy studies before they embark on mass vaccination and addresses the role of nanoparticles as carrier vehicles for these vaccines with a view to explore the present challenges and forge a path for a stronger and more viable future for the development of vaccines for SARS-CoV-2 and future pandemics. We also look at the emerging prophylactics and therapeutics in the light of ongoing cases of severe and critical COVID-19.
Coronavirus disease-19 (COVID-19) has become a pandemic, being a global health concern since December 2019 when the first cases were reported. Severe acute respiratory syndrome coronavirus 2, the COVID-19 causal agent, is a β-coronavirus that has on its surface the spike protein, which helps in its virulence and pathogenicity towards the host. Thus, effective and applicable diagnostic methods to this disease come as an important tool for the management of the patients. The use of the molecular technique PCR, which allows the detection of the viral RNA through nasopharyngeal swabs, is considered the gold standard test for the diagnosis of COVID-19. Moreover, serological methods, such as enzyme-linked immunosorbent assays and rapid tests, are able to detect severe acute respiratory syndrome coronavirus 2-specific immunoglobulin A, immunoglobulin M, and immunoglobulin G in positive patients, being important alternative techniques for the diagnostic establishment and epidemiological surveillance. On the other hand, reverse transcription loop-mediated isothermal amplification also proved to be a useful diagnostic method for the infection, mainly because it does not require a sophisticated laboratory apparatus and has similar specificity and sensitivity to PCR. Complementarily, imaging exams provide findings of typical pneumonia, such as the ground-glass opacity radiological pattern on chest computed tomography scanning, which along with laboratory tests assist in the diagnosis of COVID-19.
Species differences in the structure and function of the immune system of laboratory animals are known to exist and have been reviewed extensively. However, the number and diversity of wild and exotic species, along with their associated viruses, that come into contact with humans has increased worldwide sometimes with lethal consequences. Far less is known about the immunobiology of these exotic and wild species. Data suggest that species differences of the mechanisms of inflammation, innate immunity and adaptive immunity are all involved in the establishment and maintenance of viral infections across reservoir hosts. The current review attempts to collect relevant data concerning the basics of innate and adaptive immune functions of exotic and wild species followed by identification of those differences that may play a role in the maintenance of viral infections in reservoir hosts.
Viruses are the major pathogenic agents that cause various diseases. Antiviral drugs are used for the treatment of viral infections. Emergent advances of antiviral drugs are focused on two different approaches: targeting the host cell factors or the viruses themselves. Antiviral drugs that directly target the viruses include virus entry inhibitors, virus attachment inhibitors, uncoating inhibitors, protease inhibitors, polymerase inhibitors, nucleoside inhibitors, integrase inhibitors, and nucleotide reverse transcriptase. The protease inhibitors, viral DNA polymerase, and integrase inhibitors are the most commonly used antiviral drugs. Still, there are no effective antiviral drugs existing for several viral infections. Coronavirusdisease-2019 (COVID-19) or SARS-CoV-2 is the newest member of the corona virus family. No specific drugs particularly antiviral drugs have been approved for the treatment of COVID-19. Thus, it is extremely crucial to identify new drugs for the
treatment of the COVID-19 outbreak. Various antiviral drugs are used for COVID-
19 treatment. Currently, various drugs are under investigation to treat COVID-19 patients. Promising clinical outcomes for COVID-19 can be obtained by using alpha-interferon, remdesivir, lopinavir-ritonavir, favipiravir, ribavirin, umifenovir, oseltamivir, etc. Here, we reviewed anti-COVID-19 potencies of currently available antiviral drugs, and some antiviral drugs have been effective or prevent the spread of coronavirus.
Introduction. Recently, humanity has faced a new public
health threat – the spread of the new coronavirus in 2019
(SARS-CoV-2). To address the problems caused by the high
REVIEW ARTICLE
Epidemiological aspects in
COVID-19 infection based on
current evidences: article of
narrative synthesis
What is not known yet, about the topic
COVID-19 infection is an emerging disease that has a number
of unclear epidemiological features, such as the primary sources
of human infection, the duration of the patient’s contagiousness,
the possibility of transmitting the infection from mother
to foetus, and the specific prophylaxis of infection.
Research hypothesis
Publications addressing the epidemiological features of
COVID-19 infection could contribute to the development of
non-pharmaceutical measures for the prevention and early
localization of outbreaks of SARS-CoV-2 in conditions of community
spread.
Article’s added novelty on this scientific topic
The article summarizes the recently published articles on
the features of the spread of COVID-19 infection according to
the sources of infection, infectivity rate, routes of transmission,
risk factors related to patients age, gender, associated comorbidities,
and last but not least, trends in the development
of the effective vaccine in combating the spread of SARS-CoV-2
virus.
morbidity and mortality caused by this virus, a series of researches,
have been carried out. The aim of these researches
is to implement measures based on scientific evidence that
will help to reduce the medical, social and economic impact
worldwide.
Material and methods. The existing bibliographic source
on the PubMed platform was analysed, 251 articles, that are
related to the objectives of our research, were pre-selected,
and after excluding articles focused on clinic, treatment and
diagnosis, 72 articles relevant to the proposed research topic
were selected.
Results. The analysed bibliographic sources allowed the
highlighting of the inter-human transmission of the virus; incubation
period is 2-14 days; the reproduction index varies
from 2 to 6 infected people, depending on the prevention measures
applied; the sources of infection can be asymptomatic
persons, the most vulnerable to infection are the elderly with
co-morbidities; the virus is sensitive to the action of hydrogen
peroxide, sodium hypochlorite and alcohol over 60%. At
the same time, based on the large number of infected people,
the strategy for the development of effective vaccines against
SARS-CoV-2 is initiated.
Conclusions. At the current stage, COVID-19 infection
has caused a very high medical, social and economic impact,
becoming a pressing public health problem that needs to be
solved. Assessing the features of the epidemic process with
highlighting the epidemiological aspects, risk factors and specific
prevention measures, will contribute to reducing the cases
of infection and stabilizing the situation in the world. Despite
the fact that a number of scientific publications mention
the epidemiological features of the infection spread, there are
some moments in studies, based on outbreaks of infection recorded
under the conditions of community transmission, that
need to be elucidated.
Key words: COVID-19 infection, SARS-CoV-2 virus, source
of infection, reproduction rate, routes of transmission, risk
factors, vaccine.
Bats are the reservoir host of the novel coronavirus/SARS-CoV-2. The global pandemic worldwide infectious disease spread by the novel coronavirus caused by SARS-CoV-2 has raisedfetched the attention of scientific fraternity towards bats as a reservoir and carrier of this deadly virus. Bats are known to host hundreds of viruses; although they themselves remain unharmed. Scientific evidences revealed that bats have various immunological specializations that enabled them to remain unaffected to coronaviruses. This manuscript highlights the aspects of bats’ defense mechanism against immune system in relation to the viral load and their unique adaptability. Its The ability of bats to serve as propagating ground for viruses is favored by its extraordinary physiological traits and unique immune responses including constitutive active interferons (IFNs), dampened inflammasome response, reduced DNA sensing mechanisms, and unique B and T cell components. Furthermore, bats have evolved with their efficient mode of oxidative phosphorylation, loss of PYHIN gene family and positive selection for DNA damage checkpoints. These multiple mechanisms are detrimental for the viral have played a vital roles in the co-existence of viruses in bats and spillover events. Furthermore, we have discussed future directions to enhance knowledge and understanding of bat-human interactions and genetic diversity of bat-borne viruses, which will play a crucial role to prevent future outbreaks.
Rapid and accurate serodiagnosis is a critical component of understanding viral disease epidemiology. Typically, solid-phase immunoassays such as enzyme-linked immunosorbent assay (ELISA) are used for detecting diagnostic antibodies. However, fluid-phase immunoprecipitation assays often show higher sensitivity and specificity for assessing antibody levels. We designed and utilized a luminescent immunoprecipitation system (LIPS) for specific and sensitive detection of either severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or porcine delta coronavirus (PDCoV) antibodies. The LIPS assay efficacy and specificity was shown utilizing infected pig sera for PDCoV and commercial sera for SARS-CoV-2 and compared against cross-reactivity in commercially available or in house hyperimmune sera for multiple coronavirus antigens.
The old‐world camelids include the dromedary camel ( Camelus dromedarius ), the domesticated Bactrian camel ( Camelus bactrianus ) and the endangered wild Bactrian camel. Acceptable handling practices and restraint may vary depending on the culture and experience of the camel owners. Camel raisers should allow camel calves to live with other camels in order to develop appropriate social skills. If necessary, milk and veterinary care should be supplied by caretakers, but overly‐affectionate interaction should be avoided. Even with effective physical restraint, sedation may be necessary to perform certain tasks on camels. The doses and combinations of sedation do not vary wildly from those used in South American camelids, but some sample protocols and notes about specific drugs are included. Most camels in North America are bred by natural cover, but advanced techniques in reproduction have been developed and used with increasing frequency in the Middle East. Camels may experience lameness and bone disease due to improper dietary management.
Previous findings of Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses in bats, and the ability of Tylonycteris-BatCoV HKU4 spike protein to utilize MERS-CoV receptor, human dipeptidyl peptidase 4 hDPP4, suggest a bat ancestral origin of MERS-CoV. We developed 12 primary bat cell lines from seven bat species, including Tylonycteris pachypus, Pipistrellus abramus and Rhinolophus sinicus (hosts of Tylonycteris-BatCoV HKU4, Pipistrellus-BatCoV HKU5, and SARS-related-CoV respectively), and tested their susceptibilities to MERS-CoVs, SARS-CoV, and human coronavirus 229E (HCoV-229E). Five cell lines, including P. abramus and R. sinicus but not T. pachypus cells, were susceptible to human MERS-CoV EMC/2012. However, three tested camel MERS-CoV strains showed different infectivities, with only two strains capable of infecting three and one cell lines respectively. SARS-CoV can only replicate in R. sinicus cells, while HCoV-229E cannot replicate in any bat cells. Bat dipeptidyl peptidase 4 (DPP4) sequences were closely related to those of human and non-human primates but distinct from dromedary DPP4 sequence. Critical residues for binding to MERS-CoV spike protein were mostly conserved in bat DPP4. DPP4 was expressed in the five bat cells susceptible to MERS-CoV, with significantly higher mRNA expression levels than those in non-susceptible cells (P = 0.0174), supporting that DPP4 expression is critical for MERS-CoV infection in bats. However, overexpression of T. pachypus DPP4 failed to confer MERS-CoV susceptibility in T. pachypus cells, suggesting other cellular factors in determining viral replication. The broad cellular tropism of MERS-CoV should prompt further exploration of host diversity of related viruses to identify its ancestral origin.
The Egyptian rousette bat (ERB) is the only known Marburg virus (MARV) reservoir host. ERBs develop a productive MARV infection with low viremia and shedding but no overt disease, suggesting this virus is efficiently controlled by ERB antiviral responses. This dynamic would contrast with humans, where MARV-mediated interferon (IFN) antagonism early in infection is thought to contribute to the severe, often fatal disease. The newly-annotated ERB genome and transcriptome have now enabled us to use a custom-designed NanoString nCounter ERB CodeSet in conjunction with RNA-seq to investigate responses in a MARV-infected ERB cell line. Both transcriptomic platforms correlated well and showed that MARV inhibited the antiviral program in ERB cells, while an IFN antagonism-impaired MARV was less efficient at suppressing the response gene induction, phenotypes previously reported for primate cells. Interestingly, and despite the expansion of IFN loci in the ERB genome, neither MARV showed specific induction of almost any IFN gene. However, we detected an upregulation of putative, unannotated ERB antiviral paralogs, as well as an elevated basal expression in uninfected ERB cells of key antiviral genes.
The Middle East respiratory syndrome (MERS) is a coronavirus (CoV)-mediated respiratory disease. Virus transmission occurs within health care settings, but cases also appear sporadically in the community. Camels are believed to be the source for community-acquired cases, but most patients do not have camel exposure. Here, we assessed whether camel workers (CWs) with high rates of exposure to camel nasal and oral secretions had evidence of MERS-CoV infection. The results indicate that a high percentage of CWs were positive for virus-specific immune responses but had no history of significant respiratory disease. Thus, a possible explanation for repeated MERS outbreaks is that CWs develop mild or subclinical disease. These CWs then transmit the virus to uninfected individuals, some of whom are highly susceptible, develop severe disease, and are detected as primary MERS cases in the community.
Abstract Spillover of viruses from bats to other animals may be associated with increased contact between them, as well as increased shedding of viruses by bats. Here, we tested the prediction that little brown bats (Myotis lucifugus) co-infected with the M. lucifugus coronavirus (Myl-CoV) and with Pseudogymnoascus destructans (Pd), the fungus that causes bat white-nose syndrome (WNS), exhibit different disease severity, viral shedding and molecular responses than bats infected with only Myl-CoV or only P. destructans. We took advantage of the natural persistence of Myl-CoV in bats that were experimentally inoculated with P. destructans in a previous study. Here, we show that the intestines of virus-infected bats that were also infected with fungus contained on average 60-fold more viral RNA than bats with virus alone. Increased viral RNA in the intestines correlated with the severity of fungus-related pathology. Additionally, the intestines of bats infected with fungus exhibited different expression of mitogen-activated protein kinase pathway and cytokine related transcripts, irrespective of viral presence. Levels of coronavirus antibodies were also higher in fungal-infected bats. Our results suggest that the systemic effects of WNS may down-regulate anti-viral responses in bats persistently infected with M. lucifugus coronavirus and increase the potential of virus shedding.
Dromedary camels (Camelus dromedarius) are now known to be the vertebrate animal reservoir that intermittently transmits the Middle East respiratory syndrome coronavirus (MERS-CoV) to humans. Yet, details as to the specific mechanism(s) of zoonotic transmission from dromedaries to humans remain unclear. The aim of this study was to describe direct and indirect contact with dromedaries among all cases, and then separately for primary, non-primary, and unclassified cases of laboratory-confirmed MERS-CoV reported to the World Health Organization (WHO) between 1 January 2015 and 13 April 2018. We present any reported dromedary contact: direct, indirect, and type of indirect contact. Of all 1125 laboratory-confirmed MERS-CoV cases reported to WHO during the time period, there were 348 (30.9%) primary cases, 455 (40.4%) non-primary cases, and 322 (28.6%) unclassified cases. Among primary cases, 191 (54.9%) reported contact with dromedaries: 164 (47.1%) reported direct contact, 155 (44.5%) reported indirect contact. Five (1.1%) non-primary cases also reported contact with dromedaries. Overall, unpasteurized milk was the most frequent type of dromedary product consumed. Among cases for whom exposure was systematically collected and reported to WHO, contact with dromedaries or dromedary products has played an important role in zoonotic transmission.
Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health1. Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS)2-10. Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.
Recently, we developed a monoclonal antibody-based rapid nucleocapsid protein detection assay for diagnosis of MERS coronavirus (MERS-CoV) in humans and dromedary camels. In this study, we examined the usefulness of this assay to detect other lineage C betacoronaviruses closely related to MERS-CoV in bats. The rapid MERS-CoV nucleocapsid protein detection assay was tested positive in 24 (88.9%) of 27 Tylonycteris bat CoV HKU4 (Ty-BatCoV-HKU4) RNA-positive alimentary samples of Tylonycteris pachypus and 4 (19.0%) of 21 Pipistrellus bat CoV HKU5 (Pi-BatCoV-HKU5) RNA-positive alimentary samples of Pipistrellus abramus. There was significantly more Ty-BatCoV-HKU4 RNA-positive alimentary samples than Pi-BatCoV-HKU5 RNA-positive alimentary samples that were tested positive by the rapid MERS-CoV nucleocapsid protein detection assay (P < 0.001 by Chi-square test). The rapid assay was tested negative in all 51 alimentary samples RNA-positive for alphacoronaviruses (Rhinolophus bat CoV HKU2, Myotis bat CoV HKU6, Miniopterus bat CoV HKU8 and Hipposideros batCoV HKU10) and 32 alimentary samples positive for lineage B (SARS-related Rhinolophus bat CoV HKU3) and lineage D (Rousettus bat CoV HKU9) betacoronaviruses. No significant difference was observed between the viral loads of Ty-BatCoV-HKU4/Pi-BatCoV-HKU5 RNA-positive alimentary samples that were tested positive and negative by the rapid test (Mann-Witney U test). The rapid MERS-CoV nucleocapsid protein detection assay is able to rapidly detect lineage C betacoronaviruses in bats. It detected significantly more Ty-BatCoV-HKU4 than Pi-BatCoV-HKU5 because MERS-CoV is more closely related to Ty-BatCoV-HKU4 than Pi-BatCoV-HKU5. This assay will facilitate rapid on-site mass screening of animal samples for ancestors of MERS-CoV and tracking transmission in the related bat species.
Purpose
The first aim of this study was to develop a novel inactivated porcine epidemic diarrhea virus (PEDV) vaccine using the recently isolated Korean PEDV QIAP1401 strain and to evaluate its protective efficacy in growing pigs. The second was to determine the optimum adjuvant formulation of the inactivated PEDV vaccine that induces protection against viral challenge.
Materials and Methods
To generate high titers of infectious PEDV, the QIAP1401 isolate was passaged in Vero cells. The experimental vaccines were prepared from a binary ethyleneimine-inactivated QIAP1401 strain passaged sequentially 70 times (QIAP1401-p70), formulated with four commercial adjuvants, and administered twice intramuscularly to growing pigs. Challenge studies using a virulent homologous strain of PEDV QIAP1401-p11, which was passaged 11 times after isolation, were performed to assess protection against disease progression and viral shedding during the 15-day observation period. The vaccine-induced antibody responses were measured in serum samples collected at predetermined time points by indirect enzyme-linked immunosorbent assay and virus neutralization test.
Results
The QIAP1401-p70 strain had 42 amino acid (aa) mutations, including a 25 aa deletion, and was selected as the inactivated PEDV vaccine candidate. Although none of the pigs that received the experimental vaccines were completely protected against subsequent viral challenge, they exhibited a significantly higher immune response than did non-vaccinated control pigs. Among the vaccine groups, the highest antibody responses were observed in the pigs that received an oil-based multiphasic water/oil/water (W/O/W) emulsion adjuvanted vaccine, which delayed the onset of clinical symptoms and viral shedding.
Conclusion
A novel inactivated PEDV vaccine formulated with a W/O/W emulsion adjuvant was both immunogenic and protective against viral challenge.
Although bats are known to harbor MERS-CoV-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. While being closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Since Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can utilize MERS-CoV receptor, hDPP4, for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and utilize hDPP4. HKU25-RBD can bind to hDPP4 protein and hDPP4-expressing cells, but with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can utilize hDPP4 for entry to hDPP4-expressing cells, though with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat coronavirus spike proteins may have evolved in a stepwise manner for binding to hDPP4.
A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.
Porcine epidemic diarrhea virus strains from the G1b cluster are considered less pathogenic compared to the G2b cluster. The aim of this study was to compare the ability of G1b-based live virus exposure against use of a commercial G2b–based inactivated vaccine to protect growing pigs against G2b challenge. Thirty-nine PEDV naïve pigs were randomly divided into five groups: EXP-IM-1b (intramuscular G1b exposure; G2b challenge), EXP-ORAL-1b (oral G1b exposure; G2b challenge), VAC-IM-2b (intramuscular commercial inactivated G2b vaccination; G2b challenge), POS-CONTROL (sham-vaccination; G2b challenge) and NEG-CONTROL (sham-vaccination; sham-challenge). Pigs were vaccinated/exposed at 3 weeks of age (day post-vaccination 0, dpv 0), VAC-IM-2b pigs were revaccinated at dpv 14, and the pigs were challenged at dpv 28. Among all groups, VAC-IM-2b pigs had significantly higher anti-PEDV IgG levels on dpv 21 and 28 while EXP-ORAL-1b pigs had significantly higher anti-PEDV IgA levels on dpv 14, 21, 28 and 35. EXP-ORAL-1b also had detectable IgA in feces. Intramuscular PEDV exposure did not result in a detectable antibody response in EXP-IM-1b pigs. The fecal PEDV RNA levels in VAC-IM-2b pigs were significantly lower 5–7 days after challenge compared to the POS-CONTROL group. Under the study conditions a commercial inactivated G2b-based vaccine protected pigs against G2b challenge, as evidenced by reduction of PEDV RNA in feces for 3–4 logs during peak shedding and a shorter viral shedding duration. The oral, but not the intramuscular, experimental G1b-based live virus exposure induced a high anti-PEDV IgA response prior to challenge, which apparently did not impact PEDV shedding compared to POS-CONTROL pigs.
While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation. In vitro replication attenuation also extends to in vivo models, allowing use of dORF3-5 as a live attenuated vaccine platform. Finally, examination of ORF5 implicates a partial role in modulation of NF-κB-mediated inflammation. Together, the results demonstrate the importance of MERS-CoV accessory ORFs for pathogenesis and highlight them as potential targets for surveillance and therapeutic treatments moving forward.
IMPORTANCE The initial emergence and periodic outbreaks of MERS-CoV highlight a continuing threat posed by zoonotic pathogens to global public health. In these studies, mutant virus generation demonstrates the necessity of accessory ORFs in regard to MERS-CoV infection and pathogenesis. With this in mind, accessory ORF functions can be targeted for both therapeutic and vaccine treatments in response to MERS-CoV and related group 2C coronaviruses. In addition, disruption of accessory ORFs in parallel may offer a rapid response platform to attenuation of future emergent strains based on both SARS- and MERS-CoV accessory ORF mutants.
Since the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrom Coronavirus (MERS-CoV) it has become increasingly clear that bats are important reservoirs of CoVs. Despite this, only 6% of all CoV sequences in GenBank are from bats. The remaining 94% largely consist of known pathogens of public health or agricultural significance, indicating that current research effort is heavily biased towards describing known diseases rather than the ‘pre-emergent’ diversity in bats. Our study addresses this critical gap, and focuses on resource poor countries where the risk of zoonotic emergence is believed to be highest. We surveyed the diversity of CoVs in multiple host taxa from twenty countries to explore the factors driving viral diversity at a global scale. We identified sequences representing 100 discrete phylogenetic clusters, ninety-one of which were found in bats, and used ecological and epidemiologic analyses to show that patterns of CoV diversity correlate with those of bat diversity. This cements bats as the major evolutionary reservoirs and ecological drivers of CoV diversity. Co-phylogenetic reconciliation analysis was also used to show that host switching has contributed to CoV evolution, and a preliminary analysis suggests that regional variation exists in the dynamics of this process. Overall our study represents a model for exploring global viral diversity and advances our fundamental understanding of CoV biodiversity and the potential risk factors associated with zoonotic emergence.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) has been shown to infect both humans and dromedary camels using dipeptidyl peptidase-4 (DPP4) as its receptor. The distribution of DPP4 in the respiratory tract tissues of humans and camels reflects MERS-CoV tropism. Apart from dromedary camels, insectivorous bats are suggested as another natural reservoir for MERS-like-CoVs. In order to gain insight on the tropism of these viruses in bats, we studied the DPP4 distribution in the respiratory and extra-respiratory tissues of two frugivorous bat species (Epomophorus gambianus and Rousettus aegyptiacus) and two insectivorous bat species (Pipistrellus pipistrellus and Eptesicus serotinus). In the frugivorous bats, DPP4 was present in epithelial cells of both the respiratory and the intestinal tract, similar to what has been reported for camels and humans. In the insectivorous bats, however, DPP4 expression in epithelial cells of the respiratory tract was almost absent. The preferential expression of DPP4 in the intestinal tract of insectivorous bats, suggests that transmission of MERS-like-CoVs mainly occurs via the fecal-oral route. Our results highlight differences in the distribution of DPP4 expression among MERS-CoV susceptible species, which might influence variability in virus tropism, pathogenesis and transmission route.
The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats are likely to be the original source, as several 2c CoVs have been described from various species in the family Vespertilionidae. Here, we describe a MERS-like CoV identified from a Pipistrellus cf. hesperidus bat sampled in Uganda (strain PREDICT/PDF-2180), further supporting the hypothesis that bats are the evolutionary source of MERS-CoV. Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties. Indeed, several amino acid substitutions were identified in key binding residues that were predicted to block PREDICT/PDF-2180 from attaching to the MERS-CoV DPP4 receptor. To experimentally test this hypothesis, an infectious MERS-CoV clone expressing the PREDICT/PDF-2180 spike protein was generated. Recombinant viruses derived from the clone were replication competent but unable to spread and establish new infections in Vero cells or primary human airway epithelial cells. Our findings suggest that PREDICT/PDF-2180 is unlikely to pose a zoonotic threat. Recombination in the S1 subunit of the spike gene was identified as the primary mechanism driving variation in the spike phenotype and was likely one of the critical steps in the evolution and emergence of MERS-CoV in humans.
A high percentage (up to 90%) of dromedary camels in the Middle East as well as eastern and central Africa have antibodies to Middle East respiratory syndrome coronavirus (MERS-CoV). Here we report comparably high positivity of MERS-CoV antibodies in dromedary camels from northern Mali. This extends the range of MERS-CoV further west in Africa than reported to date and cautions that MERS-CoV should be considered in cases of severe respiratory disease in the region.
The Egyptian rousette bat (ERB) is a natural reservoir host for Marburg virus (MARV); however, the mechanisms by which MARV is transmitted bat-to-bat and to other animals are unclear. Here we co-house MARV-inoculated donor ERBs with naive contact ERBs. MARV shedding is detected in oral, rectal and urine specimens from inoculated bats from 5–19 days post infection. Simultaneously, MARV is detected in oral specimens from contact bats, indicating oral exposure to the virus. In the late study phase, we provide evidence that MARV can be horizontally transmitted from inoculated to contact ERBs by finding MARV RNA in blood and oral specimens from contact bats, followed by MARV IgG antibodies in these same bats. This study demonstrates that MARV can be horizontally transmitted from inoculated to contact ERBs, thereby providing a model for filovirus maintenance in its natural reservoir host and a potential mechanism for virus spillover to other animals.
The four human coronaviruses (HCoVs) are globally endemic respiratory pathogens. The Middle East respiratory syndrome (MERS) coronavirus (CoV) is an emerging CoV with a known zoonotic source in dromedary camels. Little is known about the origins of endemic HCoVs. Studying these viruses’ evolutionary history could provide important insight into CoV emergence. In tests of MERS-CoV–infected dromedaries, we found viruses related to an HCoV, known as HCoV-229E, in 5.6% of 1,033 animals. Human- and dromedary-derived viruses are each monophyletic, suggesting ecological isolation. One gene of dromedary viruses exists in two versions in camels, full length and deleted, whereas only the deleted version exists in humans. The deletion increased in size over a succession starting from camelid viruses via old human viruses to contemporary human viruses. Live isolates of dromedary 229E viruses were obtained and studied to assess human infection risks. The viruses used the human entry receptor aminopeptidase N and replicated in human hepatoma cells, suggesting a principal ability to cause human infections. However, inefficient replication in several mucosa-derived cell lines and airway epithelial cultures suggested lack of adaptation to the human host. Dromedary viruses were as sensitive to the human type I interferon response as HCoV-229E. Antibodies in human sera neutralized dromedary-derived viruses, suggesting population immunity against dromedary viruses. Although no current epidemic risk seems to emanate from these viruses, evolutionary inference suggests that the endemic human virus HCoV-229E may constitute a descendant of camelid-associated viruses. HCoV-229E evolution provides a scenario for MERS-CoV emergence.
Progress in combatting zoonoses that emerge from wildlife is often constrained by limited knowledge of the biology of pathogens within reservoir hosts. We focus on the host-pathogen dynamics of four emerging viruses associated with bats: Hendra, Nipah, Ebola, and Marburg viruses. Spillover of bat infections to humans and domestic animals often coincides with pulses of viral excretion within bat populations, but the mechanisms driving such pulses are unclear. Three hypotheses dominate current research on these emerging bat infections. First, pulses of viral excretion could reflect seasonal epidemic cycles driven by natural variations in population densities and contact rates among hosts. If lifelong immunity follows recovery, viruses may disappear locally but persist globally through migration; in either case, new outbreaks occur once births replenish the susceptible pool. Second, epidemic cycles could be the result of waning immunity within bats, allowing local circulation of viruses through oscillating herd immunity. Third, pulses could be generated by episodic shedding from persistently infected bats through a combination of physiological and ecological factors. The three scenarios can yield similar patterns in epidemiological surveys, but strategies to predict or manage spillover risk resulting from each scenario will be different. We outline an agenda for research on viruses emerging from bats that would allow for differentiation among the scenarios and inform development of evidence-based interventions to limit threats to human and animal health. These concepts and methods are applicable to a wide range of pathogens that affect humans, domestic animals, and wildlife.
Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs.
Bats, order Chiroptera, are one of the largest monophyletic clades in mammals. Based on morphology and behaviour bats were once differentiated into two suborders Megachiroptera and Microchiroptera Recently, researchers proposed alternative views of chiropteran classification (suborders Yinpterochiroptera and Yangochiroptera) based on morphological, molecular and fossil evidence. Since genome-scale data can significantly increase the number of informative characters for analysis, transcriptome RNA-seq data for 12 bat taxa were generated in an attempt to resolve bat subordinal relationships at the genome level. Phylogenetic reconstructions were conducted using up to 1470 orthologous genes and 634,288 aligned sites. We found strong support for the Yinpterochiroptera-Yangochiroptera classification. Next, we built expression distance matrices for each species and reconstructed gene expression trees. The tree is highly consistent with sequence-based phylogeny. We also examined the influence of taxa sampling on the performance of phylogenetic methods, and found that the topology is robust to sampling. Relaxed molecular clock estimates the divergence between Yinpterochiroptera and Yangochiroptera around 63 million years ago. The most recent common ancestor of Yinpterochiroptera, corresponding to the split between Rhinolophoidea and Pteropodidae (Old World Fruit bats), is estimated to have occurred 60 million years ago. Our work provided a valuable resource to further explore the evolutionary relationship within bats.
The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV.
Bats harbor many emerging and reemerging viruses, several of which are highly pathogenic in other mammals but cause no clinical signs of disease in bats. To determine the role of interferons (IFNs) in the ability of bats to coexist with viruses, we sequenced the type I IFN locus of the Australian black flying fox, Pteropus alecto, providing what is, to our knowledge, the first gene map of the IFN region of any bat species. Our results reveal a highly contracted type I IFN family consisting of only 10 IFNs, including three functional IFN-α loci. Furthermore, the three IFN-α genes are constitutively expressed in unstimulated bat tissues and cells and their expression is unaffected by viral infection. Constitutively expressed IFN-α results in the induction of a subset of IFN-stimulated genes associated with antiviral activity and resistance to DNA damage, providing evidence for a unique IFN system that may be linked to the ability of bats to coexist with viruses.
The Egyptian Rousette bat (Rousettus aegyptiacus), a common fruit bat species found throughout Africa and the Middle East, was recently identified as a natural reservoir host of Marburg virus. With Ebola virus, Marburg virus is a member of the family Filoviridae that causes severe hemorrhagic fever disease in humans and nonhuman primates, but results in little to no pathological consequences in bats. Understanding host-pathogen interactions within reservoir host species and how it differs from hosts that experience severe disease is an important aspect of evaluating viral pathogenesis and developing novel therapeutics and methods of prevention.
Progress in studying bat reservoir host responses to virus infection is hampered by the lack of host-specific reagents required for immunological studies. In order to establish a basis for the design of reagents, we sequenced, assembled, and annotated the R. aegyptiacus transcriptome. We performed de novo transcriptome assembly using deep RNA sequencing data from 11 distinct tissues from one male and one female bat. We observed high similarity between this transcriptome and those available from other bat species. Gene expression analysis demonstrated clustering of expression profiles by tissue, where we also identified enrichment of tissue-specific gene ontology terms. In addition, we identified and experimentally validated the expression of novel coding transcripts that may be specific to this species.
We comprehensively characterized the R. aegyptiacus transcriptome de novo. This transcriptome will be an important resource for understanding bat immunology, physiology, disease pathogenesis, and virus transmission.
Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently identified virus causing severe viral respiratory illness in people. Little is known about the reservoir in the Horn of Africa. In Kenya, where no human MERS cases have been reported, our survey of 335 dromedary camels, representing nine herds in Laikipia County, showed a high seroprevalence (46.9%) to MERS-CoV antibodies. Between herd differences were present (14.3% – 82.9%), but was not related to management type or herd isolation. Further research should focus on identifying similarity between MERS-CoV viral isolates in Kenya and clinical isolates from the Middle East and elsewhere.