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1.
Pak J Med Sci ; 36(COVID19-S4): S79-S84, 2020 May.
Article in English | MEDLINE | ID: covidwho-1726822

ABSTRACT

Coronavirus Disease 2019 (CoViD-19) is the third type of coronavirus disease after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) that appears in human population from the past two decades. It is highly contagious and rapidly spread in the human population and compelled global public health institutions on high alert. Due to genetic similarity of this novel coronavirus 2019 with bat virus its emergence from bat to humans is possible. The virus survive in the droplets of coughing and sneezing and spread around the large areas through infected person resulting in its rapid spread among people. Clinical symptoms of CoViD-19 include fever, dry cough, dyspnea, loose stool, nausea and vomiting. The present review discuss the origin of CoViD-19, its rapid spread, mortality rate and recoveries ratio around the world. Since its origin from Wuhan, the CoViD-19 spread very rapidly all across the countries, on April 17, 2020 this disease has affected 210 countries of the globe. The data obtained showed over 2.4 million confirmed cases of CoViD-19. Higher mortality rate was found in Algeria and Belgium as 15% and 13.95%, respectively. Lower mortality rate was found in Qatar 0.17% and Singapore 0.2%. Recovery versus deceased ratio showed that recovery was 68, 59 and 35 times higher than the death in Singapore, Qatar and Thailand respectively. It is concluded that 2019-novel corona virus is a zoonotic pathogen similar to MERS and SARS. Therefore, a barrier should be maintained between and across the human, household and wild animals to avoid such pandemics.

2.
J Virol ; 94(12)2020 06 01.
Article in English | MEDLINE | ID: covidwho-1723543

ABSTRACT

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that recently emerged in China is thought to have a bat origin, as its closest known relative (BatCoV RaTG13) was described previously in horseshoe bats. We analyzed the selective events that accompanied the divergence of SARS-CoV-2 from BatCoV RaTG13. To this end, we applied a population genetics-phylogenetics approach, which leverages within-population variation and divergence from an outgroup. Results indicated that most sites in the viral open reading frames (ORFs) evolved under conditions of strong to moderate purifying selection. The most highly constrained sequences corresponded to some nonstructural proteins (nsps) and to the M protein. Conversely, nsp1 and accessory ORFs, particularly ORF8, had a nonnegligible proportion of codons evolving under conditions of very weak purifying selection or close to selective neutrality. Overall, limited evidence of positive selection was detected. The 6 bona fide positively selected sites were located in the N protein, in ORF8, and in nsp1. A signal of positive selection was also detected in the receptor-binding motif (RBM) of the spike protein but most likely resulted from a recombination event that involved the BatCoV RaTG13 sequence. In line with previous data, we suggest that the common ancestor of SARS-CoV-2 and BatCoV RaTG13 encoded/encodes an RBM similar to that observed in SARS-CoV-2 itself and in some pangolin viruses. It is presently unknown whether the common ancestor still exists and, if so, which animals it infects. Our data, however, indicate that divergence of SARS-CoV-2 from BatCoV RaTG13 was accompanied by limited episodes of positive selection, suggesting that the common ancestor of the two viruses was poised for human infection.IMPORTANCE Coronaviruses are dangerous zoonotic pathogens; in the last 2 decades, three coronaviruses have crossed the species barrier and caused human epidemics. One of these is the recently emerged SARS-CoV-2. We investigated how, since its divergence from a closely related bat virus, natural selection shaped the genome of SARS-CoV-2. We found that distinct coding regions in the SARS-CoV-2 genome evolved under conditions of different degrees of constraint and are consequently more or less prone to tolerate amino acid substitutions. In practical terms, the level of constraint provides indications about which proteins/protein regions are better suited as possible targets for the development of antivirals or vaccines. We also detected limited signals of positive selection in three viral ORFs. However, we warn that, in the absence of knowledge about the chain of events that determined the human spillover, these signals should not be necessarily interpreted as evidence of an adaptation to our species.


Subject(s)
Betacoronavirus/genetics , Evolution, Molecular , Selection, Genetic , Amino Acid Sequence , Animals , Betacoronavirus/classification , COVID-19 , Chiroptera/virology , Coronavirus Infections/virology , Genome, Viral/genetics , Humans , Models, Molecular , Open Reading Frames/genetics , Pandemics , Phylogeny , Pneumonia, Viral/virology , SARS-CoV-2 , Viral Proteins/chemistry , Viral Proteins/genetics
3.
Chin Med J (Engl) ; 133(9): 1015-1024, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722617

ABSTRACT

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.


Subject(s)
Betacoronavirus , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Aged , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , SARS-CoV-2 , Tomography, X-Ray , Treatment Outcome
4.
Curr Med Chem ; 28(41): 8559-8594, 2021.
Article in English | MEDLINE | ID: covidwho-1690554

ABSTRACT

There is a new public health crisis threatening the world with the emergence and spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was later named novel coronavirus disease or COVID-19. It was then declared a pandemic by the World Health Organization on March 11, 2020. The virus originated in bats and was transmitted to humans through unknown intermediary animals in Wuhan, Hubei province, China, in December 2019. As of February 5, 2021, 103 million laboratory-confirmed cases and nearly 2.3 million deaths were reported globally. The number of death tolls continues to rise, and a large number of countries have been forced to maintain social distance in public place and enforce lockdown. As per literature, coronavirus is transmitted human to human or human to animal via airborne droplets. Coronavirus enters the human cell through the membrane ACE-2 exopeptidase receptor. WHO, ECDC, and ICMR advised avoiding public places and close contact with infected persons and pet animals. To date, there is no evidence of any effective treatment for COVID-19. The main therapies being used to treat the disease are antiviral drugs, chloroquine/hydroxychloroquine, and respiratory therapy. Although several therapies have been proposed, quarantine is the only intervention that appears to be effective in decreasing the contagion rate. We conducted a literature review of publicly available information to summarize knowledge about the pathogen and the current epidemic. In the present literature review, the causative agent of the pandemic, epidemiology, pathogenesis, and diagnostic techniques are discussed. Further, currently used treatment, preventive strategies along with vaccine trials and computational tools are all described in detail.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Communicable Disease Control , Humans , Hydroxychloroquine , Pandemics
5.
J Leukoc Biol ; 111(2): 497-508, 2022 02.
Article in English | MEDLINE | ID: covidwho-1669515

ABSTRACT

Coronaviruses (CoVs) are RNA viruses that cause human respiratory infections. Zoonotic transmission of the SARS-CoV-2 virus caused the recent COVID-19 pandemic, which led to over 2 million deaths worldwide. Elevated inflammatory responses and cytotoxicity in the lungs are associated with COVID-19 severity in SARS-CoV-2-infected individuals. Bats, which host pathogenic CoVs, operate dampened inflammatory responses and show tolerance to these viruses with mild clinical symptoms. Delineating the mechanisms governing these host-specific inflammatory responses is essential to understand host-virus interactions determining the outcome of pathogenic CoV infections. Here, we describe the essential role of inflammasome activation in determining COVID-19 severity in humans and innate immune tolerance in bats that host several pathogenic CoVs. We further discuss mechanisms leading to inflammasome activation in human SARS-CoV-2 infection and how bats are molecularly adapted to suppress these inflammasome responses. We also report an analysis of functionally important residues of inflammasome components that provide new clues of bat strategies to suppress inflammasome signaling and innate immune responses. As spillover of bat viruses may cause the emergence of new human disease outbreaks, the inflammasome regulation in bats and humans likely provides specific strategies to combat the pathogenic CoV infections.


Subject(s)
COVID-19/pathology , Immune Tolerance , Immunity, Innate , Inflammasomes/immunology , SARS-CoV-2/immunology , Animals , COVID-19/immunology , COVID-19/virology , Chiroptera , Humans , Inflammasomes/metabolism , Phylogeny
6.
J Virol ; 94(13)2020 06 16.
Article in English | MEDLINE | ID: covidwho-1583223

ABSTRACT

Fusion with, and subsequent entry into, the host cell is one of the critical steps in the life cycle of enveloped viruses. For Middle East respiratory syndrome coronavirus (MERS-CoV), the spike (S) protein is the main determinant of viral entry. Proteolytic cleavage of the S protein exposes its fusion peptide (FP), which initiates the process of membrane fusion. Previous studies on the related severe acute respiratory syndrome coronavirus (SARS-CoV) FP have shown that calcium ions (Ca2+) play an important role in fusogenic activity via a Ca2+ binding pocket with conserved glutamic acid (E) and aspartic acid (D) residues. SARS-CoV and MERS-CoV FPs share a high sequence homology, and here, we investigated whether Ca2+ is required for MERS-CoV fusion by screening a mutant array in which E and D residues in the MERS-CoV FP were substituted with neutrally charged alanines (A). Upon verifying mutant cell surface expression and proteolytic cleavage, we tested their ability to mediate pseudoparticle (PP) infection of host cells in modulating Ca2+ environments. Our results demonstrate that intracellular Ca2+ enhances MERS-CoV wild-type (WT) PP infection by approximately 2-fold and that E891 is a crucial residue for Ca2+ interaction. Subsequent electron spin resonance (ESR) experiments revealed that this enhancement could be attributed to Ca2+ increasing MERS-CoV FP fusion-relevant membrane ordering. Intriguingly, isothermal calorimetry showed an approximate 1:1 MERS-CoV FP to Ca2+ ratio, as opposed to an 1:2 SARS-CoV FP to Ca2+ ratio, suggesting significant differences in FP Ca2+ interactions of MERS-CoV and SARS-CoV FP despite their high sequence similarity.IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) is a major emerging infectious disease with zoonotic potential and has reservoirs in dromedary camels and bats. Since its first outbreak in 2012, the virus has repeatedly transmitted from camels to humans, with 2,468 confirmed cases causing 851 deaths. To date, there are no efficacious drugs and vaccines against MERS-CoV, increasing its potential to cause a public health emergency. In order to develop novel drugs and vaccines, it is important to understand the molecular mechanisms that enable the virus to infect host cells. Our data have found that calcium is an important regulator of viral fusion by interacting with negatively charged residues in the MERS-CoV FP region. This information can guide therapeutic solutions to block this calcium interaction and also repurpose already approved drugs for this use for a fast response to MERS-CoV outbreaks.


Subject(s)
Calcium/metabolism , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Host-Pathogen Interactions , Ions/metabolism , Membrane Fusion , Middle East Respiratory Syndrome Coronavirus/physiology , Virus Internalization , Amino Acid Sequence , Amino Acid Substitution , Animals , Cell Line , Chlorocebus aethiops , Humans , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Models, Molecular , Mutation , Protein Binding , Proteolysis , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Structure-Activity Relationship , Vero Cells , Virulence , Virus Assembly
7.
Transbound Emerg Dis ; 68(6): 3443-3452, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1526424

ABSTRACT

The recently emerged novel coronavirus, SARS-CoV-2, is phylogenetically related to bat coronaviruses (CoVs), specifically SARS-related CoVs from the Eurasian bat family Rhinolophidae. As this human pandemic virus has spread across the world, the potential impacts of SARS-CoV-2 on native North American bat populations are unknown, as is the ability of North American bats to serve as reservoirs or intermediate hosts able to transmit the virus to humans or to other animal species. To help determine the impacts of the pandemic virus on North American bat populations, we experimentally challenged big brown bats (Eptesicus fuscus) with SARS-CoV-2 under BSL-3 conditions. We inoculated the bats both oropharyngeally and nasally, and over the ensuing three weeks, we measured infectivity, pathology, virus concentrations in tissues, oral and rectal virus excretion, virus transmission, and clinical signs of disease. We found no evidence of SARS-CoV-2 infection in any examined bat, including no viral excretion, no transmission, no detectable virus in tissues, and no signs of disease or pathology. Based on our findings, it appears that big brown bats are resistant to infection with the SARS-CoV-2. The potential susceptibility of other North American bat species to SARS-CoV-2 remains to be investigated.


Subject(s)
COVID-19 , Chiroptera , Coronaviridae , Animals , COVID-19/veterinary , Humans , North America/epidemiology , Phylogeny , SARS-CoV-2
8.
J Virol ; 95(16): e0061721, 2021 07 26.
Article in English | MEDLINE | ID: covidwho-1486509

ABSTRACT

The current pandemic of COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the critical determinant of viral tropism and infectivity. To investigate whether naturally occurring RBD mutations during the early transmission phase have altered the receptor binding affinity and infectivity, we first analyzed in silico the binding dynamics between SARS-CoV-2 RBD mutants and the human angiotensin-converting enzyme 2 (ACE2) receptor. Among 32,123 genomes of SARS-CoV-2 isolates (December 2019 through March 2020), 302 nonsynonymous RBD mutants were identified and clustered into 96 mutant types. The six dominant mutations were analyzed applying molecular dynamics simulations (MDS). The mutant type V367F continuously circulating worldwide displayed higher binding affinity to human ACE2 due to the enhanced structural stabilization of the RBD beta-sheet scaffold. The MDS also indicated that it would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially infectious to humans. The increased infectivity of V367 mutants was further validated by performing receptor-ligand binding enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance, and pseudotyped virus assays. Phylogenetic analysis of the genomes of V367F mutants showed that during the early transmission phase, most V367F mutants clustered more closely with the SARS-CoV-2 prototype strain than the dual-mutation variants (V367F+D614G), which may derivate from recombination. The analysis of critical RBD mutations provides further insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin under negative selection pressure and supports the continuing surveillance of spike mutations to aid in the development of new COVID-19 drugs and vaccines. IMPORTANCE A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused the pandemic of COVID-19. The origin of SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether mutations in the RBD of the circulating SARS-CoV-2 isolates have altered the receptor binding affinity and made them more infectious has been the research hot spot. Given that SARS-CoV-2 is a novel coronavirus, the significance of our research is in identifying and validating the RBD mutant types emerging during the early transmission phase and increasing human angiotensin-converting enzyme 2 (ACE2) receptor binding affinity and infectivity. Our study provides insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin. The continuing surveillance of RBD mutations with increased human ACE2 affinity in human or other animals is critical to the development of new COVID-19 drugs and vaccines against these variants during the sustained COVID-19 pandemic.


Subject(s)
Amino Acid Substitution , Angiotensin-Converting Enzyme 2/genetics , COVID-19/transmission , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Binding Sites , COVID-19/pathology , COVID-19/virology , Gene Expression , Host-Pathogen Interactions/genetics , Humans , Kinetics , Molecular Dynamics Simulation , Phenylalanine/chemistry , Phenylalanine/metabolism , Phylogeny , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , SARS-CoV-2/classification , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Thermodynamics , Valine/chemistry , Valine/metabolism , Virulence , Virus Attachment
10.
Microorganisms ; 9(3)2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1389450

ABSTRACT

To prevent the emergence of zoonotic infectious diseases and reduce their epidemic potential, we need to understand their origins in nature. Bats in the order Chiroptera are widely distributed worldwide and are natural reservoirs of prominent zoonotic viruses, including Nipah virus, Marburg virus, and possibly SARS-CoV-2. In this study, we applied unbiased metagenomic and metatranscriptomic approaches to decipher the virosphere of frugivorous and insectivorous bat species captured in Guéckédou, Guinea, the epicenter of the West African Ebola virus disease epidemic in 2013-2016. Our study provides a snapshot of the viral diversity present in these bat species, with several novel viruses reported for the first time in bats, as well as some bat viruses closely related to known human or animal pathogens. In addition, analysis of Mops condylurus genomic DNA samples revealed the presence of an Ebola virus nucleoprotein (NP)-derived pseudogene inserted in its genome. These findings provide insight into the evolutionary traits of several virus families in bats and add evidence that nonretroviral integrated RNA viruses (NIRVs) derived from filoviruses may be common in bat genomes.

12.
Clin Infect Dis ; 73(2): e437-e444, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1315658

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains the furin cleavage Proline-Arginine-Arginine-Alanine (PRRA) motif in the S1/S2 region, which enhances viral pathogenicity but is absent in closely related bat and pangolin coronaviruses. Whether bat-like coronaviral variants without PRRA (∆PRRA) can establish natural infections in humans is unknown. METHODS: Here, we developed a duplex digital polymerase chain reaction assay to examine ∆PRRA variants in Vero-E6-propagated isolates, human organoids, experimentally infected hamsters, and coronavirus disease 2019 (COVID-19) patients. RESULTS: We found that SARS-CoV-2, as currently transmitting in humans, contained a quasispecies of wild-type, ∆PRRA variants and variants that have mutations upstream of the PRRA motif. Moreover, the ∆PRRA variants were readily detected despite being at a low intra-host frequency in transmitted founder viruses in hamsters and in COVID-19 patients, including in acute cases and a family cluster, with a prevalence rate of 52.9%. CONCLUSIONS: Our findings demonstrate that bat-like SARS-CoV-2ΔPRRA not only naturally exists but remains transmissible in COVID-19 patients, which has significant implications regarding the zoonotic origin and natural evolution of SARS-CoV-2.


Subject(s)
COVID-19 , Chiroptera , Alanine , Animals , Arginine , Humans , Proline , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
13.
Nat Rev Microbiol ; 19(8): 482, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275934
14.
Biochem Biophys Rep ; 26: 101023, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1272309

ABSTRACT

The outbreak of SARS in 2003, MERS in 2012, and now COVID-19 in 2019 has demonstrated that Coronaviruses are capable of causing primary lethal infections in humans, and the pandemic is now a global concern. The COVID-19 belongs to the beta coronavirus family encoding 29 proteins, of which four are structural, the Spike, Membrane, Envelope, and Nucleocapsid proteins. Here we have analyzed and compared the Membrane (M) and Envelope (E) proteins of COVID-19 and MERS with SARS and Bat viruses. The sequence analysis of conserved regions of both E and M proteins revealed that many regions of COVID-19 are similar to Bat and SARS viruses while the MERS virus showed variations. The essential binding motifs found in SARS appeared in COVID-19. Besides, the M protein of COVID-19 showed a distinct serine phosphorylation site in the C-terminal domain, which looked like a catalytic triad seen in serine proteases. A Dileucine motif occurred many times in the sequence of the M protein of all the four viruses compared. Concerning the structural part, the COVID-19 E protein showed more similarity to Bat while MERS shared similarity with the SARS virus. The M protein of both COVID-19 and MERS displayed variations in the structure. The interaction between M and E proteins was also studied to know the additional binding regions. Our study highlights the critical motifs and structural regions to be considered for further research to design better inhibitors for the infection caused by these viruses.

15.
Sci Rep ; 11(1): 7430, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1162021

ABSTRACT

Bats are known to be reservoirs of several highly pathogenic viruses. Hence, the interest in bat virus discovery has been increasing rapidly over the last decade. So far, most studies have focused on a single type of virus detection method, either PCR, virus isolation or virome sequencing. Here we present a comprehensive approach in virus discovery, using all three discovery methods on samples from the same bats. By family-specific PCR screening we found sequences of paramyxoviruses, adenoviruses, herpesviruses and one coronavirus. By cell culture we isolated a novel bat adenovirus and bat orthoreovirus. Virome sequencing revealed viral sequences of ten different virus families and orders: three bat nairoviruses, three phenuiviruses, one orbivirus, one rotavirus, one orthoreovirus, one mononegavirus, five parvoviruses, seven picornaviruses, three retroviruses, one totivirus and two thymoviruses were discovered. Of all viruses identified by family-specific PCR in the original samples, none was found by metagenomic sequencing. Vice versa, none of the viruses found by the metagenomic virome approach was detected by family-specific PCRs targeting the same family. The discrepancy of detected viruses by different detection approaches suggests that a combined approach using different detection methods is necessary for virus discovery studies.


Subject(s)
Chiroptera/virology , Genome, Viral , Virome/genetics , Animals , Chlorocebus aethiops , Germany , High-Throughput Nucleotide Sequencing , Nairovirus/classification , Nairovirus/genetics , Orbivirus/classification , Orbivirus/genetics , Phylogeny , Polymerase Chain Reaction , Rotavirus/classification , Rotavirus/genetics , Vero Cells , Viruses/classification , Viruses/genetics
16.
Bull Acad Natl Med ; 205(7): 732-736, 2021 Aug.
Article in French | MEDLINE | ID: covidwho-1252480

ABSTRACT

From the beginning of this century, three coronaviruses (CoVs) have caused severe human respiratory diseases, including severe respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and corona virus disease 2019 (COVID-19), which outbroke in 2002-2003, 2012 and 2019-2020, respectively. These viruses are three different species belonging to Coronaviridae family, Betacoronavirus genus. Discovery of closely-related CoVs in bats indicates that bats are natural reservoirs of these viruses. How and when the bat CoVs cross-species barriers to infect humans are largely understudied. This article provides an overview of the distribution, genetic evolution and interspecies transmission of bat coronaviruses in China, particularly focusing on bat SARS-related CoVs (SARSr-CoVs). Our studies showed that SARS-related CoVs are highly prevalent in horseshoe bats and some of them use the same receptor as SARS-CoV and SARS-CoV-2 and have wide cell tissue tropism. However, these bat viruses seem to be low pathogenic in human ACE2 transgenic mice compared with the SARS-CoV-2. These results imply that these bat CoVs have potential interspecies transmission to other animals and humans. Our work highlights the necessity of preparedness for future emerging infectious diseases caused by these CoVs.

17.
J Virol ; 95(15): e0049621, 2021 07 12.
Article in English | MEDLINE | ID: covidwho-1243690

ABSTRACT

The Severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 originated in bats and adapted to infect humans. Several SARS-CoV-2 strains have been identified. Genetic variation is fundamental to virus evolution and, in response to selection pressure, is manifested as the emergence of new strains and species adapted to different hosts or with novel pathogenicity. The combination of variation and selection forms a genetic footprint on the genome, consisting of the preferential accumulation of mutations in particular areas. Properties of betacoronaviruses contributing to variation and the emergence of new strains and species are beginning to be elucidated. To better understand their variation, we profiled the accumulation of mutations in all species in the genus Betacoronavirus, including SARS-CoV-2 and two other species that infect humans: SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Variation profiles identified both genetically stable and variable areas at homologous locations across species within the genus Betacoronavirus. The S glycoprotein is the most variable part of the genome and is structurally disordered. Other variable parts include proteins 3 and 7 and ORF8, which participate in replication and suppression of antiviral defense. In contrast, replication proteins in ORF1b are the least variable. Collectively, our results show that variation and structural disorder in the S glycoprotein is a general feature of all members of the genus Betacoronavirus, including SARS-CoV-2. These findings highlight the potential for the continual emergence of new species and strains with novel biological properties and indicate that the S glycoprotein has a critical role in host adaptation. IMPORTANCE Natural infection with SARS-CoV-2 and vaccines triggers the formation of antibodies against the S glycoprotein, which are detected by antibody-based diagnostic tests. Our analysis showed that variation in the S glycoprotein is a general feature of all species in the genus Betacoronavirus, including three species that infect humans: SARS-CoV, SARS-CoV-2, and MERS-CoV. The variable nature of the S glycoprotein provides an explanation for the emergence of SARS-CoV-2, the differentiation of SARS-CoV-2 into strains, and the probability of SARS-CoV-2 repeated infections in people. Variation of the S glycoprotein also has important implications for the reliability of SARS-CoV-2 antibody-based diagnostic tests and the design and deployment of vaccines and antiviral drugs. These findings indicate that adjustments to vaccine design and deployment and to antibody-based diagnostic tests are necessary to account for S glycoprotein variation.


Subject(s)
Betacoronavirus/genetics , Evolution, Molecular , Genetic Variation , Genome, Viral , Spike Glycoprotein, Coronavirus/genetics , Genome-Wide Association Study , Humans
18.
Vopr Virusol ; 66(2): 112-122, 2021 05 15.
Article in Russian | MEDLINE | ID: covidwho-1229650

ABSTRACT

Emerging and reemerging infections pose a grave global health threat. The emergence of the SARS-CoV-2 virus and the resulting COVID-19 pandemic have demonstrated the importance of studying of zoonotic viruses directly in natural foci. For SARS-like coronaviruses, as well as for many other zoonotic pathogens (including hemorrhagic fevers and rabies agents), the main reservoir are horseshoe bats (Rhinolophus spp.), which are widely distributed in Eurasia and Africa. Their range also covers the southern regions of Russia, including the North Caucasus and Crimea. Large colonies of these animals are located on the territory of Sochi National Park (SNP; subtropical zone of Krasnodar Territory, Greater Sochi region, North Caucasus). In total, according to long-term observations, up to 23 species of bats were registered here, including the great (Rh. ferrumequinum), the lesser (Rh. hipposideros), and the Mediterranean (Rh. euryale) horseshoe bats.This review provides information on zoonotic viruses associated with species of bats distributed in the subtropical zone of Krasnodar Territory of Russia, and analyzes their possible role as a natural reservoir of emerging and reemerging infections. Studying the circulation of zoonotic viruses in bats is an important element of monitoring viral populations in natural foci.


Subject(s)
Chiroptera/virology , Disease Reservoirs , Pandemics , SARS-CoV-2 , Viral Zoonoses , Animals , COVID-19/epidemiology , COVID-19/transmission , Humans , Viral Zoonoses/epidemiology , Viral Zoonoses/transmission
19.
J Mol Evol ; 89(6): 341-356, 2021 07.
Article in English | MEDLINE | ID: covidwho-1227833

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus-2 is a zoonotic virus with a possible origin in bats and potential transmission to humans through an intermediate host. When zoonotic viruses jump to a new host, they undergo both mutational and natural selective pressures that result in non-synonymous and synonymous adaptive changes, necessary for efficient replication and rapid spread of diseases in new host species. The nucleotide composition and codon usage pattern of SARS-CoV-2 indicate the presence of a highly conserved, gene-specific codon usage bias. The codon usage pattern of SARS-CoV-2 is mostly antagonistic to human and bat codon usage. SARS-CoV-2 codon usage bias is mainly shaped by the natural selection, while mutational pressure plays a minor role. The time-series analysis of SARS-CoV-2 genome indicates that the virus is slowly evolving. Virus isolates from later stages of the outbreak have more biased codon usage and nucleotide composition than virus isolates from early stages of the outbreak.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Codon Usage/genetics , Evolution, Molecular , Host-Pathogen Interactions/genetics , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Adaptation, Physiological/genetics , Animals , COVID-19/transmission , Chiroptera/genetics , Genome, Viral/genetics , Humans , Mutation , Pandemics , Principal Component Analysis , Selection, Genetic/genetics , Time Factors , Virus Replication
20.
Transbound Emerg Dis ; 2021 May 12.
Article in English | MEDLINE | ID: covidwho-1225689

ABSTRACT

The vampire bat (Desmodus rotundus) is a haematophagous animal that feeds exclusively on the blood of domestic mammals. Vampire bat feeding habits enable their contact with mammalian hosts and may enhance zoonotic spillover. Moreover, they may carry several pathogenic organisms, including coronaviruses (CoVs), for which they are important hosts. The human pathogens that cause severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV) and possibly coronavirus disease 2019 (SARS-CoV-2) all originated in bats but required bridge hosts to spread into human populations. To monitor the presence of potential zoonotic viruses in bats, the present work evaluated the presence of CoVs in vampire bats from southern Brazil. A total of 101 vampire bats were captured and euthanized between 2017 and 2019 in Rio Grande do Sul state, southern Brazil. The brain, heart, liver, lungs, kidneys and intestines were collected and macerated individually. The samples were pooled and submitted to high-throughput sequencing (HTS) using the Illumina MiSeq platform and subsequently individually screened using a pancoronavirus RT-PCR protocol. We detected CoV-related sequences in HTS, but only two (2/101; 1.98%) animals had CoV detected in the intestines by RT-PCR. Partial sequences of RdRp and spike genes were obtained in the same sample and the RdRp region in the other sample. The sequences were classified as belonging to Alphacoronavirus. The sequences were closely related to alphacoronaviruses detected in vampire bats from Peru. The continuous monitoring of bat CoVs may help to map and predict putative future zoonotic agents with great impacts on human health.

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