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1.
J Proteome Res ; 19(4): 1351-1360, 2020 04 03.
Article in English | MEDLINE | ID: covidwho-688546

ABSTRACT

As the infection of 2019-nCoV coronavirus is quickly developing into a global pneumonia epidemic, the careful analysis of its transmission and cellular mechanisms is sorely needed. In this Communication, we first analyzed two recent studies that concluded that snakes are the intermediate hosts of 2019-nCoV and that the 2019-nCoV spike protein insertions share a unique similarity to HIV-1. However, the reimplementation of the analyses, built on larger scale data sets using state-of-the-art bioinformatics methods and databases, presents clear evidence that rebuts these conclusions. Next, using metagenomic samples from Manis javanica, we assembled a draft genome of the 2019-nCoV-like coronavirus, which shows 73% coverage and 91% sequence identity to the 2019-nCoV genome. In particular, the alignments of the spike surface glycoprotein receptor binding domain revealed four times more variations in the bat coronavirus RaTG13 than in the Manis coronavirus compared with 2019-nCoV, suggesting the pangolin as a missing link in the transmission of 2019-nCoV from bats to human.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/virology , Genome, Viral/genetics , Host-Pathogen Interactions , Models, Molecular , Pneumonia, Viral/virology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Amino Acid Sequence , Animals , Betacoronavirus/classification , Eutheria/virology , HIV-1/genetics , Humans , Metagenome , Pandemics , Protein Structure, Tertiary , Sequence Alignment , Sequence Analysis, Protein , Snakes/virology
2.
J Infect Dis ; 222(2): 223-233, 2020 06 29.
Article in English | MEDLINE | ID: covidwho-656287

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-CoV) was discovered as a novel pathogen in the 2002-2003 SARS epidemic. The emergence and disappearance of this pathogen have brought questions regarding its source and evolution. Within the genome sequences of 281 SARS-CoVs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-related CoVs (SARSr-CoVs), a ~430 bp genomic region (from 27 701 bp to 28 131 bp in AY390556.1) with regular variations was investigated. This ~430 bp region overlaps with the ORF8 gene and is prone to deletions and nucleotide substitutions. Its complexity suggested the need for a new genotyping method for coronaviruses related to SARS-similar coronaviruses (SARS-CoV, SARSr-CoV, and SARS-CoV-2). Bat SARSr-CoV presented 3 genotypes, of which type 0 is only seen in bat SARSr-CoV, type I is present in SARS in the early phase, and type II is found in all SARS-CoV-2. This genotyping also shows potential usage in distinguishing the SARS-similar coronaviruses from different hosts and geographic areas. This genomic region has important implications for predicting the epidemic trend and studying the evolution of coronavirus.


Subject(s)
Betacoronavirus/genetics , Genome, Viral , SARS Virus/genetics , Viral Matrix Proteins/genetics , Animals , Base Sequence , Chiroptera/virology , Eutheria/virology , Evolution, Molecular , Genes, Viral , Genetic Variation , Humans , Open Reading Frames , Phylogeny , Sequence Alignment , Sequence Deletion , Spike Glycoprotein, Coronavirus/genetics , Viverridae/virology
3.
Genomics ; 112(5): 3226-3237, 2020 09.
Article in English | MEDLINE | ID: covidwho-597640

ABSTRACT

A global emergency due to the COVID-19 pandemic demands various studies related to genes and genomes of the SARS-CoV2. Among other important proteins, the role of accessory proteins are of immense importance in replication, regulation of infections of the coronavirus in the hosts. The largest accessory protein in the SARS-CoV2 genome is ORF3a which modulates the host response to the virus infection and consequently it plays an important role in pathogenesis. In this study, an attempt is made to decipher the conservation of nucleotides, dimers, codons and amino acids in the ORF3a genes across thirty-two genomes of Indian patients. ORF3a gene possesses single and double point mutations in Indian SARS-CoV2 genomes suggesting the change of SARS-CoV2's virulence property in Indian patients. We find that the parental origin of the ORF3a gene over the genomes of SARS-CoV2 and Pangolin-CoV is same from the phylogenetic analysis based on conservation of nucleotides and so on. This study highlights the accumulation of mutation on ORF3a in Indian SARS-CoV2 genomes which may provide the designing therapeutic approach against SARS-CoV2.


Subject(s)
Betacoronavirus/genetics , Conserved Sequence , Coronavirus Infections/virology , Mutation , Pneumonia, Viral/virology , Viral Regulatory and Accessory Proteins/genetics , Animals , Base Sequence , Biological Evolution , Chiroptera/virology , Coronavirus Infections/veterinary , Eutheria/virology , Genome, Viral , Genomics , Humans , India , Pandemics , Phylogeny , Viral Regulatory and Accessory Proteins/chemistry , Viral Structural Proteins/chemistry , Viral Structural Proteins/genetics
4.
Biomed Res Int ; 2020: 4389089, 2020.
Article in English | MEDLINE | ID: covidwho-618728

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.


Subject(s)
Betacoronavirus/chemistry , Coronavirus Infections/virology , Pneumonia, Viral/virology , Viral Envelope Proteins/chemistry , Viral Matrix Proteins/chemistry , Alphacoronavirus/chemistry , Alphacoronavirus/classification , Alphacoronavirus/genetics , Amino Acid Sequence , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , Chiroptera/virology , Coronaviridae/chemistry , Coronaviridae/classification , Coronaviridae/genetics , Eutheria/virology , Humans , Models, Molecular , Pandemics , Protein Conformation , Sequence Homology, Amino Acid , Species Specificity , Structural Homology, Protein , Viral Envelope Proteins/genetics , Viral Matrix Proteins/genetics
5.
Mol Biol Rep ; 47(6): 4827-4833, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-277073

ABSTRACT

Pangolins, or scaly anteaters, have recently been flagshiped as one of the most illegally traded mammals, and as a corollary, as potential intermediate hosts at the origin of the COVID-19 pandemic. In order to improve the traceability of their trade, we developed 20 polymorphic microsatellite loci for the white-bellied pangolin (Phataginus tricuspis), the species most frequently found on African bushmeat markets. We genotyped 24 white-bellied pangolins from the Douala market, Cameroon, originating from the Ebo forest c. 75 km north-east of Douala. The number of alleles per locus ranged from 4 to 12 (mean = 6.95), and mean observed and expected heterozygosities were 0.592 (0.208-0.875) and 0.671 (0.469-0.836), respectively. Genetic diversity was higher than that cross-estimated from microsatellite loci developed for other species of pangolins. Two loci deviated from Hardy-Weinberg equilibrium and two loci showed linkage disequilibrium. Genetic variance (PCoA) was increased with the addition of 13 pangolins of unknown origin, possibly suggesting that the Douala market is fed from differentiated source populations of white-bellied pangolins. Each of the 37 individuals had a unique multilocus genotype. The unbiased probability of identity (uPI) and the probability of identity among siblings (PIsibs) were both very low (uPI = 8.443 e-21; PIsibs = 1.011 e-07). Only five microsatellite loci were needed to reach the conservative value of PIsibs < 0.01, overall indicating a powerful discriminating power of our combined loci. These 20 newly developed microsatellite loci might prove useful in tracing the local-to-global trade of the white-bellied pangolin, and will hopefully contribute to the DNA-assisted implementation of future conservation strategies at reasonable costs.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/transmission , Eutheria/genetics , Microsatellite Repeats , Pandemics , Pneumonia, Viral/transmission , Zoonoses/transmission , Alleles , Animals , Cameroon/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Disease Reservoirs/virology , Eutheria/virology , Female , Genetic Loci , Genetic Markers , Genotype , Humans , Linkage Disequilibrium , Male , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/virology , Zoonoses/epidemiology , Zoonoses/prevention & control , Zoonoses/virology
6.
PLoS Pathog ; 16(5): e1008421, 2020 05.
Article in English | MEDLINE | ID: covidwho-260623

ABSTRACT

The outbreak of a novel corona Virus Disease 2019 (COVID-19) in the city of Wuhan, China has resulted in more than 1.7 million laboratory confirmed cases all over the world. Recent studies showed that SARS-CoV-2 was likely originated from bats, but its intermediate hosts are still largely unknown. In this study, we assembled the complete genome of a coronavirus identified in 3 sick Malayan pangolins. The molecular and phylogenetic analyses showed that this pangolin coronavirus (pangolin-CoV-2020) is genetically related to the SARS-CoV-2 as well as a group of bat coronaviruses but do not support the SARS-CoV-2 emerged directly from the pangolin-CoV-2020. Our study suggests that pangolins are natural hosts of Betacoronaviruses. Large surveillance of coronaviruses in pangolins could improve our understanding of the spectrum of coronaviruses in pangolins. In addition to conservation of wildlife, minimizing the exposures of humans to wildlife will be important to reduce the spillover risks of coronaviruses from wild animals to humans.


Subject(s)
Betacoronavirus/classification , Betacoronavirus/genetics , Coronavirus Infections/virology , Disease Reservoirs/virology , Eutheria/virology , Pneumonia, Viral/virology , Animals , Coronaviridae/classification , Coronaviridae/genetics , Host Specificity , Humans , Pandemics , Phylogeny , Sequence Homology, Nucleic Acid , Zoonoses/prevention & control , Zoonoses/virology
7.
Curr Biol ; 30(11): 2196-2203.e3, 2020 06 08.
Article in English | MEDLINE | ID: covidwho-232567

ABSTRACT

The unprecedented pandemic of pneumonia caused by a novel coronavirus, SARS-CoV-2, in China and beyond has had major public health impacts on a global scale [1, 2]. Although bats are regarded as the most likely natural hosts for SARS-CoV-2 [3], the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomic analysis of samples from 227 bats collected from Yunnan Province in China between May and October 2019. Notably, RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 at the scale of the complete virus genome and 97.2% identity in the 1ab gene, in which it is the closest relative of SARS-CoV-2 reported to date. In contrast, RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor-binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein. This provides strong evidence that such insertion events can occur naturally in animal betacoronaviruses.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Chiroptera/virology , Mutagenesis, Insertional , Spike Glycoprotein, Coronavirus/genetics , Amino Acid Sequence , Animals , Betacoronavirus/chemistry , Eutheria/virology , Feces/virology , Genome, Viral , Models, Molecular , Phylogeny , RNA, Viral/genetics , SARS Virus/genetics , Sequence Alignment , Sequence Analysis, RNA , Spike Glycoprotein, Coronavirus/chemistry
8.
Nature ; 583(7815): 286-289, 2020 07.
Article in English | MEDLINE | ID: covidwho-210764

ABSTRACT

The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Eutheria/virology , Evolution, Molecular , Genome, Viral/genetics , Sequence Homology, Nucleic Acid , Animals , Betacoronavirus/classification , China , Chiroptera/virology , Chlorocebus aethiops , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Coronavirus Infections/transmission , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Disease Reservoirs/virology , Genomics , Host Specificity , Humans , Lung/pathology , Lung/virology , Malaysia , Nucleocapsid Proteins/genetics , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Polymerase Chain Reaction , Recombination, Genetic , Sequence Alignment , Sequence Analysis, RNA , Spike Glycoprotein, Coronavirus/genetics , Vero Cells , Viral Envelope Proteins/genetics , Viral Matrix Proteins/genetics , Zoonoses/transmission , Zoonoses/virology
10.
mSphere ; 5(3)2020 05 06.
Article in English | MEDLINE | ID: covidwho-186537

ABSTRACT

In numerous instances, tracking the biological significance of a nucleic acid sequence can be augmented through the identification of environmental niches in which the sequence of interest is present. Many metagenomic data sets are now available, with deep sequencing of samples from diverse biological niches. While any individual metagenomic data set can be readily queried using web-based tools, meta-searches through all such data sets are less accessible. In this brief communication, we demonstrate such a meta-metagenomic approach, examining close matches to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in all high-throughput sequencing data sets in the NCBI Sequence Read Archive accessible with the "virome" keyword. In addition to the homology to bat coronaviruses observed in descriptions of the SARS-CoV-2 sequence (F. Wu, S. Zhao, B. Yu, Y. M. Chen, et al., Nature 579:265-269, 2020, https://doi.org/10.1038/s41586-020-2008-3; P. Zhou, X. L. Yang, X. G. Wang, B. Hu, et al., Nature 579:270-273, 2020, https://doi.org/10.1038/s41586-020-2012-7), we note a strong homology to numerous sequence reads in metavirome data sets generated from the lungs of deceased pangolins reported by Liu et al. (P. Liu, W. Chen, and J. P. Chen, Viruses 11:979, 2019, https://doi.org/10.3390/v11110979). While analysis of these reads indicates the presence of a similar viral sequence in pangolin lung, the similarity is not sufficient to either confirm or rule out a role for pangolins as an intermediate host in the recent emergence of SARS-CoV-2. In addition to the implications for SARS-CoV-2 emergence, this study illustrates the utility and limitations of meta-metagenomic search tools in effective and rapid characterization of potentially significant nucleic acid sequences.IMPORTANCE Meta-metagenomic searches allow for high-speed, low-cost identification of potentially significant biological niches for sequences of interest.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/veterinary , Eutheria/virology , Lung Diseases/veterinary , Metagenomics/methods , Animals , Base Sequence , Chiroptera/virology , Coronavirus Infections/virology , Lung/virology , Lung Diseases/virology , Sequence Alignment
11.
J Med Virol ; 92(6): 602-611, 2020 06.
Article in English | MEDLINE | ID: covidwho-153847

ABSTRACT

To investigate the evolutionary history of the recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China, a total of 70 genomes of virus strains from China and elsewhere with sampling dates between 24 December 2019 and 3 February 2020 were analyzed. To explore the potential intermediate animal host of the SARS-CoV-2 virus, we reanalyzed virome data sets from pangolins and representative SARS-related coronaviruses isolates from bats, with particular attention paid to the spike glycoprotein gene. We performed phylogenetic, split network, transmission network, likelihood-mapping, and comparative analyses of the genomes. Based on Bayesian time-scaled phylogenetic analysis using the tip-dating method, we estimated the time to the most recent common ancestor and evolutionary rate of SARS-CoV-2, which ranged from 22 to 24 November 2019 and 1.19 to 1.31 × 10-3 substitutions per site per year, respectively. Our results also revealed that the BetaCoV/bat/Yunnan/RaTG13/2013 virus was more similar to the SARS-CoV-2 virus than the coronavirus obtained from the two pangolin samples (SRR10168377 and SRR10168378). We also identified a unique peptide (PRRA) insertion in the human SARS-CoV-2 virus, which may be involved in the proteolytic cleavage of the spike protein by cellular proteases, and thus could impact host range and transmissibility. Interestingly, the coronavirus carried by pangolins did not have the RRAR motif. Therefore, we concluded that the human SARS-CoV-2 virus, which is responsible for the recent outbreak of COVID-19, did not come directly from pangolins.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Genome, Viral , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Spike Glycoprotein, Coronavirus/genetics , Amino Acid Sequence , Animals , Betacoronavirus/classification , Betacoronavirus/pathogenicity , Chiroptera/virology , Coronavirus Infections/virology , Eutheria/virology , Evolution, Molecular , Host Specificity , Humans , Phylogeny , Pneumonia, Viral/virology , Sequence Alignment , Sequence Homology, Amino Acid , Spike Glycoprotein, Coronavirus/classification , Spike Glycoprotein, Coronavirus/metabolism
14.
Nature ; 581(7807): 221-224, 2020 05.
Article in English | MEDLINE | ID: covidwho-19453

ABSTRACT

A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-191,2. A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor-angiotensin-converting enzyme 2 (ACE2)-in humans3,4. Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD-ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2.


Subject(s)
Betacoronavirus/chemistry , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Receptors, Virus/chemistry , Receptors, Virus/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Zoonoses/virology , Animals , Betacoronavirus/drug effects , Betacoronavirus/metabolism , Binding Sites , China/epidemiology , Chiroptera/virology , Coronavirus/chemistry , Coronavirus/isolation & purification , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Crystallization , Crystallography, X-Ray , Disease Reservoirs/virology , Eutheria/virology , Humans , Models, Molecular , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Protein Binding , Protein Domains , Protein Stability , SARS Virus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Zoonoses/epidemiology , Zoonoses/transmission
15.
Nature ; 583(7815): 282-285, 2020 07.
Article in English | MEDLINE | ID: covidwho-17844

ABSTRACT

The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Eutheria/virology , Evolution, Molecular , Genome, Viral/genetics , Sequence Homology, Nucleic Acid , Amino Acid Sequence , Animals , Betacoronavirus/chemistry , Betacoronavirus/classification , China/epidemiology , Chiroptera/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Disease Reservoirs/virology , Genomics , Humans , Malaysia , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Recombination, Genetic , Sequence Alignment , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Zoonoses/virology
16.
Curr Biol ; 30(7): 1346-1351.e2, 2020 04 06.
Article in English | MEDLINE | ID: covidwho-10553

ABSTRACT

An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in the city of Wuhan in China and has widely spread worldwide. Currently, it is vital to explore potential intermediate hosts of SARS-CoV-2 to control COVID-19 spread. Therefore, we reinvestigated published data from pangolin lung samples from which SARS-CoV-like CoVs were detected by Liu et al. [1]. We found genomic and evolutionary evidence of the occurrence of a SARS-CoV-2-like CoV (named Pangolin-CoV) in dead Malayan pangolins. Pangolin-CoV is 91.02% and 90.55% identical to SARS-CoV-2 and BatCoV RaTG13, respectively, at the whole-genome level. Aside from RaTG13, Pangolin-CoV is the most closely related CoV to SARS-CoV-2. The S1 protein of Pangolin-CoV is much more closely related to SARS-CoV-2 than to RaTG13. Five key amino acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and SARS-CoV-2, but four amino acid mutations are present in RaTG13. Both Pangolin-CoV and RaTG13 lost the putative furin recognition sequence motif at S1/S2 cleavage site that can be observed in the SARS-CoV-2. Conclusively, this study suggests that pangolin species are a natural reservoir of SARS-CoV-2-like CoVs.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Disease Reservoirs/virology , Eutheria/virology , Pneumonia, Viral/virology , Amino Acid Sequence , Animals , Chiroptera , Genome, Viral , Malaysia , Pandemics , Phylogeny , Sequence Alignment , Spike Glycoprotein, Coronavirus/chemistry
19.
J Med Virol ; 92(6): 595-601, 2020 06.
Article in English | MEDLINE | ID: covidwho-2181

ABSTRACT

From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) crossed the species barriers to infect humans, causing thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS-CoV-2), which has become the cause of the outbreak of Coronavirus Disease 2019 (COVID-19), was discovered. Until 18 February 2020, there were 72 533 confirmed COVID-19 cases (including 10 644 severe cases) and 1872 deaths in China. SARS-CoV-2 is spreading among the public and causing substantial burden due to its human-to-human transmission. However, the intermediate host of SARS-CoV-2 is still unclear. Finding the possible intermediate host of SARS-CoV-2 is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor-binding domain (RBD) of coronavirus spike protein and the host receptor, angiotensin-converting enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that, other than pangolins and snakes, as previously suggested, turtles (Chrysemys picta bellii, Chelonia mydas, and Pelodiscus sinensis) may act as the potential intermediate hosts transmitting SARS-CoV-2 to humans.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Pandemics , Peptidyl-Dipeptidase A/chemistry , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Receptors, Virus/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Amino Acid Sequence , Animals , Betacoronavirus/classification , Betacoronavirus/pathogenicity , Binding Sites , China/epidemiology , Chiroptera/virology , Coronavirus Infections/virology , Eutheria/virology , Humans , Models, Molecular , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Phylogeny , Pneumonia, Viral/virology , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , Protein Interaction Mapping , Receptors, Virus/genetics , Receptors, Virus/metabolism , Sequence Alignment , Sequence Homology, Amino Acid , Snakes/virology , Spike Glycoprotein, Coronavirus/classification , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Turtles/virology
20.
Viruses ; 12(2)2020 02 22.
Article in English | MEDLINE | ID: covidwho-1449

ABSTRACT

After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as "coronavirus disease 2019" (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pneumonia, Viral , SARS Virus , Severe Acute Respiratory Syndrome , Animals , Betacoronavirus/chemistry , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , China/epidemiology , Chiroptera/virology , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Coronavirus Infections/virology , Disease Reservoirs , Disease Susceptibility , Eutheria/virology , Genome, Viral , Global Health , Humans , Infectious Disease Incubation Period , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Proteome , SARS Virus/chemistry , SARS Virus/genetics , SARS Virus/pathogenicity , Sequence Alignment , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/therapy , Severe Acute Respiratory Syndrome/virology , Viral Proteins
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