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1.
Nature ; 603(7903): 913-918, 2022 03.
Article in English | MEDLINE | ID: covidwho-1671589

ABSTRACT

Two different sarbecoviruses have caused major human outbreaks in the past two decades1,2. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain2-6. However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses7-11. Here we use high-throughput assays12 to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable-for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern12 but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.


Subject(s)
Angiotensin-Converting Enzyme 2 , Evolution, Molecular , SARS Virus , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Binding Sites , COVID-19/virology , Chiroptera/virology , Humans , Protein Binding , SARS Virus/classification , SARS Virus/genetics , SARS Virus/metabolism , SARS-CoV-2/chemistry , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
2.
Viruses ; 14(1)2022 01 09.
Article in English | MEDLINE | ID: covidwho-1611142

ABSTRACT

We found and genetically described two novel SARS-like coronaviruses in feces and oral swabs of the greater (R. ferrumequinum) and the lesser (R. hipposideros) horseshoe bats in southern regions of Russia. The viruses, named Khosta-1 and Khosta-2, together with related viruses from Bulgaria and Kenya, form a separate phylogenetic lineage. We found evidence of recombination events in the evolutionary history of Khosta-1, which involved the acquisition of the structural proteins S, E, and M, as well as the nonstructural genes ORF3, ORF6, ORF7a, and ORF7b, from a virus that is related to the Kenyan isolate BtKY72. The examination of bats by RT-PCR revealed that 62.5% of the greater horseshoe bats in one of the caves were positive for Khosta-1 virus, while its overall prevalence was 14%. The prevalence of Khosta-2 was 1.75%. Our results show that SARS-like coronaviruses circulate in horseshoe bats in the region, and we provide new data on their genetic diversity.


Subject(s)
Chiroptera/virology , SARS Virus/genetics , Animals , Base Sequence , Chiroptera/classification , Evolution, Molecular , Feces/virology , Metagenomics , Mouth/virology , Phylogeny , Prevalence , Recombination, Genetic , Russia , SARS Virus/classification , Species Specificity , Spike Glycoprotein, Coronavirus/genetics , Viral Proteins/genetics
3.
Sci Rep ; 11(1): 17365, 2021 08 30.
Article in English | MEDLINE | ID: covidwho-1379334

ABSTRACT

The SARS-CoV-2 pandemic prompts evaluation of recombination in human coronavirus (hCoV) evolution. We undertook recombination analyses of 158,118 public seasonal hCoV, SARS-CoV-1, SARS-CoV-2 and MERS-CoV genome sequences using the RDP4 software. We found moderate evidence for 8 SARS-CoV-2 recombination events, two of which involved the spike gene, and low evidence for one SARS-CoV-1 recombination event. Within MERS-CoV, 229E, OC43, NL63 and HKU1 datasets, we noted 7, 1, 9, 14, and 1 high-confidence recombination events, respectively. There was propensity for recombination breakpoints in the non-ORF1 region of the genome containing structural genes, and recombination severely skewed the temporal structure of these data, especially for NL63 and OC43. Bayesian time-scaled analyses on recombinant-free data indicated the sampled diversity of seasonal CoVs emerged in the last 70 years, with 229E displaying continuous lineage replacements. These findings emphasize the importance of genomic based surveillance to detect recombination in SARS-CoV-2, particularly if recombination may lead to immune evasion.


Subject(s)
Middle East Respiratory Syndrome Coronavirus/genetics , Recombination, Genetic , SARS Virus/genetics , SARS-CoV-2/genetics , Bayes Theorem , Databases, Genetic , Genome, Viral , Humans , Immune Evasion , Middle East Respiratory Syndrome Coronavirus/classification , SARS Virus/classification , SARS-CoV-2/classification , Spike Glycoprotein, Coronavirus/genetics , Viral Nonstructural Proteins/genetics
4.
Emerg Microbes Infect ; 10(1): 1507-1514, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1310873

ABSTRACT

Severe respiratory disease coronavirus-2 (SARS-CoV-2) has been the most devastating disease COVID-19 in the century. One of the unsolved scientific questions of SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbour highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). This study identified a novel lineage of SARSr-CoVs, including RaTG15 and seven other viruses, from bats at the same location where we found RaTG13 in 2015. Although RaTG15 and the related viruses share 97.2% amino acid sequence identities with SARS-CoV-2 in the conserved ORF1b region, it only shows less than 77.6% nucleotide identity to all known SARSr-CoVs at the genome level, thus forming a distinct lineage in the Sarbecovirus phylogenetic tree. We found that the RaTG15 receptor-binding domain (RBD) can bind to ACE2 from Rhinolophus affinis, Malayan pangolin, and use it as an entry receptor, except for ACE2 from humans. However, it contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we showed that none of the known viruses in bat SARSr-CoV-2 lineage discovered uses human ACE2 as efficiently as the pangolin-derived SARSr-CoV-2 or some viruses in the SARSr-CoV-1 lineage. Therefore, further systematic and longitudinal studies in bats are needed to prevent future spillover events caused by SARSr-CoVs or to understand the origin of SARS-CoV-2 better.


Subject(s)
Angiotensin-Converting Enzyme 2/physiology , Cell Lineage , Chiroptera/virology , SARS Virus/isolation & purification , SARS-CoV-2/classification , Animals , Host Specificity , Phylogeny , SARS Virus/classification
5.
Bioessays ; 43(7): e2100015, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1245362

ABSTRACT

RaTG13, MP789, and RmYN02 are the strains closest to SARS-CoV-2, and their existence came to light only after the start of the pandemic. Their genomes have been used to support a natural origin of SARS-CoV-2 but after a close examination all of them exhibit several issues. We specifically address the presence in RmYN02 and closely related RacCSxxx strains of a claimed natural PAA/PVA amino acid insertion at the S1/S2 junction of their spike protein at the same position where the PRRA insertion in SARS-CoV-2 has created a polybasic furin cleavage site. We show that RmYN02/RacCSxxx instead of the claimed insertion carry a 6-nucleotide deletion in the region and that the 12-nucleotide insertion in SARS-CoV-2 remains unique among Sarbecoviruses. Also, our analysis of RaTG13 and RmYN02's metagenomic datasets found unexpected reads which could indicate possible contamination. Because of their importance to inferring SARS-CoV-2's origin, we call for a careful reevaluation of RaTG13, MP789 and RmYN02 sequencing records and assembly methods.


Subject(s)
COVID-19/virology , Chiroptera/virology , Pangolins/virology , SARS Virus/genetics , SARS-CoV-2/classification , SARS-CoV-2/genetics , Uncertainty , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/epidemiology , COVID-19/transmission , Datasets as Topic , Furin/metabolism , Humans , Pandemics , Phylogeny , SARS Virus/classification , SARS Virus/isolation & purification , SARS-CoV-2/isolation & purification , Sequence Deletion/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Viral Zoonoses/transmission , Viral Zoonoses/virology
6.
J Mol Med (Berl) ; 99(1): 93-106, 2021 01.
Article in English | MEDLINE | ID: covidwho-956167

ABSTRACT

In humans, coronaviruses can cause infections of the respiratory system, with damage of varying severity depending on the virus examined: ranging from mild-to-moderate upper respiratory tract diseases, such as the common cold, pneumonia, severe acute respiratory syndrome, kidney failure, and even death. Human coronaviruses known to date, common throughout the world, are seven. The most common-and least harmful-ones were discovered in the 1960s and cause a common cold. Others, more dangerous, identified in the early 2000s and cause more severe respiratory tract infections. Among these the SARS-CoV, isolated in 2003 and responsible for the severe acute respiratory syndrome (the so-called SARS), which appeared in China in November 2002, the coronavirus 2012 (2012-nCoV) cause of the Middle Eastern respiratory syndrome (MERS) from coronavirus, which exploded in June 2012 in Saudi Arabia, and actually SARS-CoV-2. On December 31, 2019, a new coronavirus strain was reported in Wuhan, China, identified as a new coronavirus beta strain ß-CoV from group 2B, with a genetic similarity of approximately 70% to SARS-CoV, the virus responsible of SARS. In the first half of February, the International Committee on Taxonomy of Viruses (ICTV), in charge of the designation and naming of the viruses (i.e., species, genus, family, etc.), thus definitively named the new coronavirus as SARS-CoV-2. This article highlights the main knowledge we have about the biomolecular and pathophysiologic mechanisms of SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/genetics , COVID-19/metabolism , COVID-19/virology , China , Coronavirus Infections/classification , Coronavirus Infections/genetics , Coronavirus Infections/metabolism , Humans , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/metabolism , SARS Virus/classification , SARS Virus/genetics , SARS Virus/metabolism , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/metabolism
7.
Biochem Biophys Res Commun ; 538: 24-34, 2021 01 29.
Article in English | MEDLINE | ID: covidwho-921830

ABSTRACT

Two pandemics of respiratory distress diseases associated with zoonotic introductions of the species Severe acute respiratory syndrome-related coronavirus in the human population during 21st century raised unprecedented interest in coronavirus research and assigned it unseen urgency. The two viruses responsible for the outbreaks, SARS-CoV and SARS-CoV-2, respectively, are in the spotlight, and SARS-CoV-2 is the focus of the current fast-paced research. Its foundation was laid down by studies of many corona- and related viruses that collectively form the vast order Nidovirales. Comparative genomics of nidoviruses played a key role in this advancement over more than 30 years. It facilitated the transfer of knowledge from characterized to newly identified viruses, including SARS-CoV and SARS-CoV-2, as well as contributed to the dissection of the nidovirus proteome and identification of patterns of variations between different taxonomic groups, from species to families. This review revisits selected cases of protein conservation and variation that define nidoviruses, illustrates the remarkable plasticity of the proteome during nidovirus adaptation, and asks questions at the interface of the proteome and processes that are vital for nidovirus reproduction and could inform the ongoing research of SARS-CoV-2.


Subject(s)
Coronaviridae Infections/virology , Nidovirales/classification , Nidovirales/genetics , Conserved Sequence , Evolution, Molecular , Genetic Variation , Genomics , Humans , Phylogeny , Proteome , SARS Virus/classification , SARS Virus/genetics , SARS-CoV-2/classification , SARS-CoV-2/genetics , Viral Proteins
8.
Genomics ; 113(1 Pt 2): 778-784, 2021 01.
Article in English | MEDLINE | ID: covidwho-867194

ABSTRACT

The coronavirus pandemic became a major risk in global public health. The outbreak is caused by SARS-CoV-2, a member of the coronavirus family. Though the images of the virus are familiar to us, in the present study, an attempt is made to hear the coronavirus by translating its protein spike into audio sequences. The musical features such as pitch, timbre, volume and duration are mapped based on the coronavirus protein sequence. Three different viruses Influenza, Ebola and Coronavirus were studied and compared through their auditory virus sequences by implementing Haar wavelet transform. The sonification of the coronavirus benefits in understanding the protein structures by enhancing the hidden features. Further, it makes a clear difference in the representation of coronavirus compared with other viruses, which will help in various research works related to virus sequence. This evolves as a simplified and novel way of representing the conventional computational methods.


Subject(s)
Algorithms , COVID-19/virology , Genome, Viral , Music , SARS-CoV-2/classification , SARS-CoV-2/genetics , Wavelet Analysis , Amino Acid Sequence , Cluster Analysis , Coronavirus/classification , Coronavirus/genetics , Ebolavirus/classification , Ebolavirus/genetics , Humans , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/genetics , Orthomyxoviridae/classification , Orthomyxoviridae/genetics , Pandemics , RNA, Viral/genetics , SARS Virus/classification , SARS Virus/genetics , Viral Proteins/genetics
9.
Cell Death Dis ; 11(9): 799, 2020 09 24.
Article in English | MEDLINE | ID: covidwho-796027

ABSTRACT

A severe upper respiratory tract syndrome caused by the new coronavirus has now spread to the entire world as a highly contagious pandemic. The large scale explosion of the disease is conventionally traced back to January of this year in the Chinese province of Hubei, the wet markets of the principal city of Wuhan being assumed to have been the specific causative locus of the sudden explosion of the infection. A number of findings that are now coming to light show that this interpretation of the origin and history of the pandemic is overly simplified. A number of variants of the coronavirus would in principle have had the ability to initiate the pandemic well before January of this year. However, even if the COVID-19 had become, so to say, ready, conditions in the local environment would have had to prevail to induce the loss of the biodiversity's "dilution effect" that kept the virus under control, favoring its spillover from its bat reservoir to the human target. In the absence of these appropriate conditions only abortive attempts to initiate the pandemic could possibly occur: a number of them did indeed occur in China, and probably elsewhere as well. These conditions were unfortunately present at the wet marked in Wuhan at the end of last year.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , SARS Virus/pathogenicity , Severe Acute Respiratory Syndrome/epidemiology , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , COVID-19 , Chiroptera/virology , Coronavirus Infections/transmission , Eutheria/virology , Humans , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Phylogeny , Pneumonia, Viral/transmission , Protein Binding , SARS Virus/classification , SARS Virus/genetics , SARS-CoV-2 , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Severe Acute Respiratory Syndrome/transmission , Severity of Illness Index , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Viverridae/virology
10.
Open Vet J ; 10(2): 164-177, 2020 08.
Article in English | MEDLINE | ID: covidwho-724486

ABSTRACT

Viruses are having great time as they seem to have bogged humans down. Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and novel coronavirus (COVID-19) are the three major coronaviruses of present-day global human and animal health concern. COVID-19 caused by SARS-CoV-2 is identified as the newest disease, presumably of bat origin. Different theories on the evolution of viruses are in circulation, yet there is no denying the fact that the animal source is the skeleton. The whole world is witnessing the terror of the COVID-19 pandemic that is following the same path of SARS and MERS, and seems to be more severe. In addition to humans, several species of animals are reported to have been infected with these life-threatening viruses. The possible routes of transmission and their zoonotic potentialities are the subjects of intense research. This review article aims to overview the link of all these three deadly coronaviruses among animals along with their phylogenic evolution and cross-species transmission. This is essential since animals as pets or food are said to pose some risk, and their better understanding is a must in order to prepare a possible plan for future havoc in both human and animal health. Although COVID-19 is causing a human health hazard globally, its reporting in animals are limited compared to SARS and MERS. Non-human primates and carnivores are most susceptible to SARS-coronavirus and SARS-CoV-2, respectively, whereas the dromedary camel is susceptible to MERS-coronavirus. Phylogenetically, the trio viruses are reported to have originated from bats and have special capacity to undergo mutation and genomic recombination in order to infect humans through its reservoir or replication host. However, it is difficult to analyze how the genomic pattern of coronaviruses occurs. Thus, increased possibility of new virus-variants infecting humans and animals in the upcoming days seems to be the biggest challenge for the future of the world. One health approach is portrayed as our best way ahead, and understanding the animal dimension will go a long way in formulating such preparedness plans.


Subject(s)
Betacoronavirus/classification , Coronavirus Infections/veterinary , Middle East Respiratory Syndrome Coronavirus/classification , Pandemics/veterinary , Pneumonia, Viral/veterinary , SARS Virus/classification , Severe Acute Respiratory Syndrome/veterinary , Animals , Animals, Wild , Betacoronavirus/genetics , COVID-19 , Camelids, New World/virology , Camelus/virology , Cats , Chiroptera/virology , Coronavirus Infections/immunology , Coronavirus Infections/transmission , Disease Susceptibility/veterinary , Dogs , Eutheria/virology , Ferrets/virology , Humans , Lions/virology , Middle East Respiratory Syndrome Coronavirus/genetics , Phylogeny , Pneumonia, Viral/immunology , Pneumonia, Viral/transmission , Primates/virology , Raccoon Dogs/virology , SARS Virus/genetics , SARS-CoV-2 , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/transmission , Snakes/virology , Tigers/virology , Viverridae/virology
11.
Infect Genet Evol ; 85: 104502, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-712141

ABSTRACT

Human Coronaviruses (HCoV), periodically emerging across the world, are potential threat to humans such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) - diseases termed as COVID-19. Current SARS-CoV-2 outbreak have fueled ongoing efforts to exploit various viral target proteins for therapy, but strategies aimed at blocking the viral proteins as in drug and vaccine development have largely failed. In fact, evidence has now shown that coronaviruses undergoes rapid recombination to generate new strains of altered virulence; additionally, escaped the host antiviral defense system and target humoral immune system which further results in severe deterioration of the body such as by cytokine storm. This demands the understanding of phenotypic and genotypic classification, and pathogenesis of SARS-CoV-2 for the production of potential therapy. In lack of clear clinical evidences for the pathogenesis of COVID-19, comparative analysis of previous pandemic HCoVs associated immunological responses can provide insights into COVID-19 pathogenesis. In this review, we summarize the possible origin and transmission mode of CoVs and the current understanding on the viral genome integrity of known pandemic virus against SARS-CoV-2. We also consider the host immune response and viral evasion based on available clinical evidences which would be helpful to remodel COVID-19 pathogenesis; and hence, development of therapeutics against broad spectrum of coronaviruses.


Subject(s)
Coronavirus Infections/transmission , SARS Virus/pathogenicity , SARS-CoV-2/pathogenicity , Animals , Genome, Viral , Humans , Pandemics , Phylogeny , SARS Virus/chemistry , SARS Virus/classification , SARS Virus/genetics , SARS-CoV-2/chemistry , SARS-CoV-2/classification , SARS-CoV-2/genetics , Virulence
12.
Virol J ; 17(1): 117, 2020 07 29.
Article in English | MEDLINE | ID: covidwho-684739

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has spread rapidly across the world and become an international public health emergency. Both SARS-CoV-2 and SARS-CoV belong to subfamily Coronavirinae in the family Coronaviridae of the order Nidovirales and they are classified as the SARS-like species while belong to different cluster. Besides, viral structure, epidemiology characteristics and pathological characteristics are also different. We present a comprehensive survey of the latest coronavirus-SARS-CoV-2-from investigating its origin and evolution alongside SARS-CoV. Meanwhile, pathogenesis, cardiovascular disease in COVID-19 patients, myocardial injury and venous thromboembolism induced by SARS-CoV-2 as well as the treatment methods are summarized in this review.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Angiotensin-Converting Enzyme 2 , Antiviral Agents/therapeutic use , Asymptomatic Infections , Betacoronavirus/chemistry , Betacoronavirus/classification , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , COVID-19 , Comorbidity , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/therapy , Disease Susceptibility , Evolution, Molecular , Genome, Viral , Humans , Immunization, Passive , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/therapy , Receptors, Coronavirus , Receptors, Virus/metabolism , SARS Virus/chemistry , SARS Virus/classification , SARS Virus/pathogenicity , SARS Virus/physiology , SARS-CoV-2 , Viral Proteins/chemistry
13.
Genes (Basel) ; 11(7)2020 07 07.
Article in English | MEDLINE | ID: covidwho-639723

ABSTRACT

The pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure. Here, we analyzed mutation patterns in 34 human SARS-CoV-2 isolates and a closely related RaTG13 isolated from Rhinolophus affinis (a horseshoe bat). We also evaluated the CpG dinucleotide contents in SARS-CoV-2 and other human and animal coronavirus genomes. Out of 1136 single nucleotide variations (~4% divergence) between human SARS-CoV-2 and bat RaTG13, 682 (60%) can be attributed to C>U and U>C substitutions, far exceeding other types of substitutions. An accumulation of C>U mutations was also observed in SARS-CoV2 variants that arose within the human population. Globally, the C>U substitutions increased the frequency of codons for hydrophobic amino acids in SARS-CoV-2 peptides, while U>C substitutions decreased it. In contrast to most other coronaviruses, both SARS-CoV-2 and RaTG13 exhibited CpG depletion in their genomes. The data suggest that C-to-U conversion mediated by C deamination played a significant role in the evolution of the SARS-CoV-2 coronavirus. We hypothesize that the high frequency C>U transitions reflect virus adaptation processes in their hosts, and that SARS-CoV-2 could have been evolving for a relatively long period in humans following the transfer from animals before spreading worldwide.


Subject(s)
Betacoronavirus/genetics , Cytosine/metabolism , Evolution, Molecular , SARS Virus/genetics , Uracil/metabolism , Animals , Base Sequence , Betacoronavirus/classification , Betacoronavirus/isolation & purification , Chiroptera/virology , CpG Islands , Humans , Phylogeny , Polymorphism, Single Nucleotide , SARS Virus/classification , SARS Virus/isolation & purification , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
14.
Rev Med Virol ; 30(5): e2122, 2020 09.
Article in English | MEDLINE | ID: covidwho-621806

ABSTRACT

Coronavirus (CoV) disease 2019 (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome CoV 2 (SARS-CoV-2). The highly contagious SARS-CoV-2 belongs to the genus Betacoronavirus, and it is phylogenetically closely related to SARS-CoV, a human CoV that caused an outbreak back in 2002 to 2003. Both SARS-CoV-2 and SARS-CoV enter human cells via the interactions between viral crown-like spike protein and human angiotensin-converting enzyme 2 (ACE2) receptor. Here, we aim to review the involvement of ACE2 in human CoV infections by discussing the roles of ACE2 in CoV evolution, cross-species transmissibility, and COVID-19 susceptibility. We also provide our perspectives on COVID-19 treatment and prevention.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/virology , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/virology , Receptors, Virus/genetics , SARS Virus/genetics , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/classification , Betacoronavirus/pathogenicity , Biological Evolution , COVID-19 , Chiroptera/virology , Coronavirus Infections/physiopathology , Eutheria/virology , Gene Expression Regulation , Humans , Pandemics , Peptidyl-Dipeptidase A/metabolism , Phylogeny , Pneumonia, Viral/physiopathology , Protein Binding , Receptors, Virus/metabolism , SARS Virus/classification , SARS Virus/pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/physiopathology , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization
15.
Infect Genet Evol ; 84: 104440, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-621792

ABSTRACT

SARS-CoV-2, a new coronavirus strain responsible for COVID-19, has emerged in Wuhan City, China, and continuing its global pandemic nature. The availability of the complete gene sequences of the virus helps to know about the origin and molecular characteristics of this virus. In the present study, we performed bioinformatic analysis of the available gene sequence data of SARS-CoV-2 for the understanding of evolution and molecular characteristics and immunogenic resemblance of the circulating viruses. Phylogenetic analysis was performed for four types of representative viral proteins (spike, membrane, envelope and nucleoprotein) of SARS-CoV-2, HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HKU1, MERS-CoV, HKU4, HKU5 and BufCoV-HKU26. The findings demonstrated that SARS-CoV-2 exhibited convergent evolutionary relation with previously reported SARS-CoV. It was also depicted that SARS-CoV-2 proteins were highly similar and identical to SARS-CoV proteins, though proteins from other coronaviruses showed a lower level of resemblance. The cross-checked conservancy analysis of SARS-CoV-2 antigenic epitopes showed significant conservancy with antigenic epitopes derived from SARS-CoV. Descriptive epidemiological analysis on several epidemiological indices was performed on available epidemiological outbreak information from several open databases on COVID-19 (SARS-CoV-2). Satellite-derived imaging data have been employed to understand the role of temperature in the environmental persistence of the virus. Findings of the descriptive analysis were used to describe the global impact of newly emerged SARS-CoV-2, and the risk of an epidemic in Bangladesh.


Subject(s)
Antigens, Viral/genetics , Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Genome, Viral , Pandemics , Pneumonia, Viral/epidemiology , SARS Virus/genetics , Spike Glycoprotein, Coronavirus/chemistry , Alphacoronavirus/classification , Alphacoronavirus/genetics , Alphacoronavirus/metabolism , Amino Acid Sequence , Animals , Antigens, Viral/chemistry , Antigens, Viral/metabolism , Bangladesh/epidemiology , Base Sequence , Betacoronavirus/classification , Betacoronavirus/metabolism , Binding Sites , COVID-19 , Chiroptera/virology , Computational Biology , Coronavirus 229E, Human/classification , Coronavirus 229E, Human/genetics , Coronavirus 229E, Human/metabolism , Coronavirus Infections/virology , Coronavirus NL63, Human/classification , Coronavirus NL63, Human/genetics , Coronavirus NL63, Human/metabolism , Coronavirus OC43, Human/classification , Coronavirus OC43, Human/genetics , Coronavirus OC43, Human/metabolism , Humans , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/metabolism , Models, Molecular , Mutation , Nucleoproteins/chemistry , Nucleoproteins/genetics , Nucleoproteins/metabolism , Phylogeny , Pneumonia, Viral/virology , Protein Binding , Protein Interaction Domains and Motifs , SARS Virus/classification , SARS Virus/metabolism , SARS-CoV-2 , Sequence Alignment , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Viral Envelope Proteins/chemistry , Viral Envelope Proteins/genetics , Viral Envelope Proteins/metabolism
16.
Infect Genet Evol ; 84: 104389, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-459162

ABSTRACT

The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected in S, 12 variations were located at the N-terminal domain (NTD) and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin-converting enzyme 2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.


Subject(s)
Alphacoronavirus/genetics , Betacoronavirus/genetics , Genome, Viral , Peptidyl-Dipeptidase A/chemistry , SARS Virus/genetics , Spike Glycoprotein, Coronavirus/chemistry , Alphacoronavirus/classification , Alphacoronavirus/metabolism , Angiotensin-Converting Enzyme 2 , Animals , Base Sequence , Betacoronavirus/classification , Betacoronavirus/metabolism , Binding Sites , Chiroptera/virology , Gene Expression , Humans , Models, Molecular , Mutation , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , SARS Virus/classification , SARS Virus/metabolism , SARS-CoV-2 , Sequence Alignment , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Structural Homology, Protein , Virus Attachment
17.
J Med Virol ; 92(6): 688-692, 2020 06.
Article in English | MEDLINE | ID: covidwho-8355

ABSTRACT

The city of Wuhan, Hubei province, China, was the origin of a severe pneumonia outbreak in December 2019, attributed to a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), causing a total of 2761 deaths and 81109 cases (25 February 2020). SARS-CoV-2 belongs to genus Betacoronavirus, subgenus Sarbecovirus. The polyprotein 1ab (pp1ab) remains unstudied thoroughly since it is similar to other sarbecoviruses. In this short communication, we performed phylogenetic-structural sequence analysis of pp1ab protein of SARS-CoV-2. The analysis showed that the viral pp1ab has not changed in most isolates throughout the outbreak time, but interestingly a deletion of 8 aa in the virulence factor nonstructural protein 1 was found in a virus isolated from a Japanese patient that did not display critical symptoms. While comparing pp1ab protein with other betacoronaviruses, we found a 42 amino acid signature that is only present in SARS-CoV-2 (AS-SCoV2). Members from clade 2 of sarbecoviruses have traces of this signature. The AS-SCoV2 located in the acidic-domain of papain-like protein of SARS-CoV-2 and bat-SL-CoV-RatG13 guided us to suggest that the novel 2019 coronavirus probably emerged by genetic drift from bat-SL-CoV-RaTG13. The implication of this amino acid signature in papain-like protein structure arrangement and function is something worth to be explored.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , SARS Virus/genetics , Viral Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Betacoronavirus/classification , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , COVID-19 , Chiroptera/microbiology , Computational Biology/methods , Coronavirus Infections/transmission , Coronavirus Infections/virology , Coronavirus Papain-Like Proteases , Evolution, Molecular , Gene Expression , Humans , Papain/genetics , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Polyproteins , SARS Virus/classification , SARS Virus/pathogenicity , SARS-CoV-2 , Sequence Alignment , Sequence Homology, Amino Acid , Viral Nonstructural Proteins/genetics
18.
J Med Virol ; 92(6): 660-666, 2020 06.
Article in English | MEDLINE | ID: covidwho-7544

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease with fatal outcomes. In this study, a fundamental knowledge gap question is to be resolved by evaluating the differences in biological and pathogenic aspects of SARS-CoV-2 and the changes in SARS-CoV-2 in comparison with the two prior major COV epidemics, SARS and Middle East respiratory syndrome (MERS) coronaviruses. METHODS: The genome composition, nucleotide analysis, codon usage indices, relative synonymous codons usage, and effective number of codons (ENc) were analyzed in the four structural genes; Spike (S), Envelope (E), membrane (M), and Nucleocapsid (N) genes, and two of the most important nonstructural genes comprising RNA-dependent RNA polymerase and main protease (Mpro) of SARS-CoV-2, Beta-CoV from pangolins, bat SARS, MERS, and SARS CoVs. RESULTS: SARS-CoV-2 prefers pyrimidine rich codons to purines. Most high-frequency codons were ending with A or T, while the low frequency and rare codons were ending with G or C. SARS-CoV-2 structural proteins showed 5 to 20 lower ENc values, compared with SARS, bat SARS, and MERS CoVs. This implies higher codon bias and higher gene expression efficiency of SARS-CoV-2 structural proteins. SARS-CoV-2 encoded the highest number of over-biased and negatively biased codons. Pangolin Beta-CoV showed little differences with SARS-CoV-2 ENc values, compared with SARS, bat SARS, and MERS CoV. CONCLUSION: Extreme bias and lower ENc values of SARS-CoV-2, especially in Spike, Envelope, and Mpro genes, are suggestive for higher gene expression efficiency, compared with SARS, bat SARS, and MERS CoVs.


Subject(s)
Betacoronavirus/genetics , Cysteine Endopeptidases/genetics , Middle East Respiratory Syndrome Coronavirus/genetics , Nucleocapsid Proteins/genetics , RNA-Dependent RNA Polymerase/genetics , SARS Virus/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/genetics , Viral Nonstructural Proteins/genetics , Animals , Base Sequence , Betacoronavirus/classification , Betacoronavirus/pathogenicity , COVID-19 , Chiroptera/microbiology , Codon Usage , Computational Biology , Coronavirus 3C Proteases , Coronavirus Envelope Proteins , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Coronavirus Nucleocapsid Proteins , Cysteine Endopeptidases/metabolism , Eutheria/microbiology , Gene Expression , Humans , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Nucleocapsid Proteins/metabolism , Pandemics , Phosphoproteins , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , RNA-Dependent RNA Polymerase/metabolism , SARS Virus/classification , SARS Virus/pathogenicity , SARS-CoV-2 , Sequence Homology, Nucleic Acid , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/transmission , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/metabolism , Viral Envelope Proteins/metabolism , Viral Nonstructural Proteins/metabolism
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