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1.
Viruses ; 15(1):170, 2023.
Article in English | ProQuest Central | ID: covidwho-2216949

ABSTRACT

Pseudorabies virus (PRV) generally infects pigs and threatens the pig industry. However, recently we have isolated a PRV strain designated hSD-1/2019 from infected humans. In this study, we compared the complete genome sequence of hSD-1/2019 with those of pig-originated PRV strains. Sequence alignments revealed that the genome sequence of hSD-1/2019 was highly homologous to those of the porcine PRV strains. Phylogenetic analyses found that hSD-1/2019 was the closest related to porcine PRV endemic strains in China, particularly the variant strains circulating recently. We also showed that the glycoproteins important for the multiplication and pathogenesis of hSD-1/2019 were highly similar to those of the pig endemic strains. Diversifying selection analyses revealed that hSD-1/2019 and pig variant strains are under diversifying selection. Recombination analysis indicated that hSD-1/2019 was a recombinant of several PRV variant strains and an earlier PRV classic strain. Finally, we found that both human and pig-originated PRV strains could induce cytopathic effects in cells from humans, pigs, and mice, but only the human PRV and pig-variant PRV formed large syncytia in human cell lines. The data presented in this study contribute to our understanding of the molecular basis for the pathogenesis of human PRV from a genomic aspect.

2.
Front Microbiol ; 13: 922393, 2022.
Article in English | MEDLINE | ID: covidwho-2065588

ABSTRACT

Coronavirus disease 2019 (COVID-19) has been a pandemic disease reported in almost every country and causes life-threatening, severe respiratory symptoms. Recent studies showed that various environmental selection pressures challenge the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infectivity and, in response, the virus engenders new mutations, leading to the emergence of more virulent strains of WHO concern. Advance prediction of the forthcoming virulent SARS-CoV-2 strains in response to the principal environmental selection pressures like temperature and solar UV radiation is indispensable to overcome COVID-19. To discover the UV-solar radiation-driven genomic adaption of SARS-CoV-2, a curated dataset of 2,500 full-grade genomes from five different UVindex regions (25 countries) was subjected to in-depth downstream genome-wide analysis. The recurrent variants that best respond to UV-solar radiations were extracted and extensively annotated to determine their possible effects and impacts on gene functions. This study revealed 515 recurrent single nucleotide variants (rcntSNVs) as SARS-CoV-2 genomic responses to UV-solar radiation, of which 380 were found to be distinct. For all discovered rcntSNVs, 596 functional effects (rcntEffs) were detected, containing 290 missense, 194 synonymous, 81 regulatory, and 31 in the intergenic region. The highest counts of missense rcntSNVs in spike (27) and nucleocapsid (26) genes explain the SARS-CoV-2 genomic adjustment to escape immunity and prevent UV-induced DNA damage, respectively. Among all, the most commonly observed rcntEffs were four missenses (RdRp-Pro327Leu, N-Arg203Lys, N-Gly204Arg, and Spike-Asp614Gly) and one synonymous (ORF1ab-Phe924Phe) functional effects. The highest number of rcntSNVs found distinct and were uniquely attributed to the specific UVindex regions, proposing solar-UV radiation as one of the driving forces for SARS-CoV-2 differential genomic adaptation. The phylogenetic relationship indicated the high UVindex region populating SARS-CoV-2 as the recent progenitor of all included samples. Altogether, these results provide baseline genomic data that may need to be included for preparing UVindex region-specific future diagnostic and vaccine formulations.

3.
Genome Biol ; 23(1): 182, 2022 08 29.
Article in English | MEDLINE | ID: covidwho-2038853

ABSTRACT

With the arrival of telomere-to-telomere (T2T) assemblies of the human genome comes the computational challenge of efficiently and accurately constructing multiple genome alignments at an unprecedented scale. By identifying nucleotides across genomes which share a common ancestor, multiple genome alignments commonly serve as the bedrock for comparative genomics studies. In this review, we provide an overview of the algorithmic template that most multiple genome alignment methods follow. We also discuss prospective areas of improvement of multiple genome alignment for keeping up with continuously arriving high-quality T2T assembled genomes and for unlocking clinically-relevant insights.


Subject(s)
Genome, Human , Genomics , Genomics/methods , Humans , Nucleotides , Telomere/genetics
4.
BMC Genomics ; 23(1): 510, 2022 Jul 14.
Article in English | MEDLINE | ID: covidwho-1933076

ABSTRACT

BACKGROUND: The SARS-CoV-2 virus is responsible for the COVID-19 pandemic. To better understand the evolution of SARS-CoV-2 early in the pandemic in the Province of Cordoba, Argentina, we performed a comparative genomic analysis of SARS-CoV-2 strains detected in survivors and non-survivors of COVID-19. We also carried out an epidemiological study to find a possible association between the symptoms and comorbidities of these patients with their clinical outcomes. RESULTS: A representative sampling was performed in different cities in the Province of Cordoba. Ten and nine complete SARS-CoV-2 genomes were obtained by next-generation sequencing of nasopharyngeal specimens from non-survivors and survivors, respectively. Phylogenetic and phylodynamic analyses revealed multiple introductions of the most common lineages in South America, including B.1, B.1.1.1, B.1.499, and N.3. Fifty-six mutations were identified, with 14% of those in common between the non-survivor and survivor groups. Specific SARS-CoV-2 mutations for survivors constituted 25% whereas for non-survivors they were 41% of the repertoire, indicating partial selectivity. The non-survivors' variants showed higher diversity in 9 genes, with a majority in Nsp3, while the survivors' variants were detected in 5 genes, with a higher incidence in the Spike protein. At least one comorbidity was present in 60% of non-survivor patients and 33% of survivors. Age 75-85 years (p = 0.018) and hospitalization (p = 0.019) were associated with non-survivor patients. Related to the most common symptoms, the prevalence of fever was similar in both groups, while dyspnea was more frequent among non-survivors and cough among survivors. CONCLUSIONS: This study describes the association of clinical characteristics with the clinical outcomes of survivors and non-survivors of COVID-19 patients, and the specific mutations found in the genome sequences of SARS-CoV-2 in each patient group. Future research on the functional characterization of novel mutations should be performed to understand the role of these variations in SARS-CoV-2 pathogenesis and COVID-19 disease outcomes. These results add new genomic data to better understand the evolution of the SARS-CoV-2 variants that spread in Argentina during the first wave of the COVID-19 pandemic.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Aged, 80 and over , Argentina/epidemiology , COVID-19/epidemiology , Genome, Viral , Genomics , Humans , Pandemics , Phylogeny , SARS-CoV-2/genetics
5.
Viruses ; 14(6)2022 05 26.
Article in English | MEDLINE | ID: covidwho-1869814

ABSTRACT

In silico methods for immune epitope prediction have become essential for vaccine and therapeutic design, but manual intra-species comparison of putative epitopes remains challenging and subject to human error. Created initially for analyzing SARS-CoV-2 variants of concern, comparative analysis of variant epitope sequences (CAVES) is a novel tool designed to carry out rapid comparative analyses of epitopes amongst closely related pathogens, substantially reducing the required time and user workload. CAVES applies a two-level analysis approach. The Level-one (L1) analysis compares two epitope prediction files, and the Level-two (L2) analysis incorporates search results from the IEDB database of experimentally confirmed epitopes. Both L1 and L2 analyses sort epitopes into categories of exact matches, partial matches, or novel epitopes based on the degree to which they match with peptides from the compared file. Furthermore, CAVES uses positional sequence data to improve its accuracy and speed, taking only a fraction of the time required by manual analyses and minimizing human error. CAVES is widely applicable for evolutionary analyses and antigenic comparisons of any closely related pathogen species. CAVES is open-source software that runs through a graphical user interface on Windows operating systems, making it widely accessible regardless of coding expertise. The CAVES source code and test dataset presented here are publicly available on the CAVES GitHub page.


Subject(s)
COVID-19 , SARS-CoV-2 , Computational Biology/methods , Epitopes/genetics , Epitopes, T-Lymphocyte , Humans , SARS-CoV-2/genetics , Software
6.
Infect Genet Evol ; 101: 105282, 2022 07.
Article in English | MEDLINE | ID: covidwho-1783642

ABSTRACT

BACKGROUND: The massive increase in COVID-19 infection had generated a second wave in India during May-June 2021 with a critical pandemic situation. The Delta variant (B.1.617.2) was a significant factor during the second wave. Conversely, the UK had passed through the crucial phase of the pandemic from November to December 2020 due to B.1.1.7. The study tried to comprehend the pandemic response in the UK and India to the spread of the B.1.1.7 (Alpha, UK) variant and B.1.617.2 (Delta, India) variant. METHODS: This study was performed in three directions to understand the pandemic response of the two emerging variants. First, we served comparative genomics, such as genome sequence submission patterns, mutational landscapes, and structural landscapes of significant mutations (N501Y, D614G, L452R, E484Q, and P681R). Second, we performed evolutionary epidemiology using molecular phylogenetics, scatter plots of the cluster evaluation, country-wise transmission pattern, and frequency pattern. Third, the receptor binding pattern was analyzed using the Wuhan reference strain and the other two variants. RESULTS: The study analyzed the country-wise and region-wise genome sequences and their submission pattern, molecular phylogenetics, scatter plot of the cluster evaluation, country-wise geographical distribution and transmission pattern, frequency pattern, entropy diversity, and mutational landscape of the two variants. The structural pattern was analyzed in the N501Y, D614G L452R, E484Q, and P681R mutations. The study found increased molecular interactivity between hACE2-RBD binding of B.1.1.7 and B.1.617.2 compared to the Wuhan reference strain. Our receptor binding analysis showed a similar indication pattern for hACE2-RBD of these two variants. However, B.1.617.2 offers slightly better stability in the hACE2-RBD binding pattern through MD simulation than B.1.1.7. CONCLUSION: The increased hACE2-RBD binding pattern of B.1.1.7 and B.1.617.2 might help to increase the infectivity compared to the Wuhan reference strain.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , COVID-19/epidemiology , Genomics , Humans , Mutation , Pandemics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/metabolism , United Kingdom/epidemiology
7.
2nd International Conference on Big Data Economy and Information Management, BDEIM 2021 ; : 313-317, 2021.
Article in English | Scopus | ID: covidwho-1774573

ABSTRACT

Since the coronavirus (SARS-CoV-2) outbreak in 2019, it has infected millions of people and claimed the lives of tens of thousands of people. During the coronavirus pandemic, big data and its applications have become one of the few powerful means to fight the virus. Nowadays, many countries and research institutions are using big data and its applications to track and control the spread of the contagious disease. In the future, people can use big data to fight against such epidemics. For example, comparative genomic research on virus variants, accelerated by big data analysis, can yield important information about virus mutations and evolutionary selection. This article mainly discusses the application of big data during the COVID-19 pandemic and how to fight similar epidemics in the future. Software and applications have been developed based on big data to track and predict infections. IoT -based solutions have been deployed in preliminary diagnosis. Therefore, in similar epidemics in the future, big data can accelerate tracking, prediction, diagnosis, and treatment, which helps the government and experts make more informed decisions to fight the virus and reduce its social impact. © 2021 IEEE.

8.
Bioessays ; 43(12): e2100194, 2021 12.
Article in English | MEDLINE | ID: covidwho-1482114

ABSTRACT

The causative agent of COVID-19 SARS-CoV-2 has led to over 4 million deaths worldwide. Understanding the origin of this coronavirus is important for the prevention of future outbreaks. The dominant point of view that the virus transferred to humans either directly from bats or through an intermediate mammalian host has been challenged by Segreto and Deigin, who claim that the genome of SARS-CoV-2 has certain features suggestive of its artificial creation. Following their response to our commentary, here we continue the discussion of the proposed arguments for this hypothesis. We show that neither the existence of a furin cleavage site in SARS-CoV-2, nor the presence of specific sequences within the nucleotide insertion encoding that site are evidence for intelligent design. We also explain why existing genetic data, viral diversity and past human history suggest that a natural origin of the virus is the most likely scenario. Genetic evidence suggesting otherwise is yet to be presented.


Subject(s)
COVID-19 , Chiroptera , Animals , Humans , Laboratories , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
9.
Virus Res ; 304: 198526, 2021 10 15.
Article in English | MEDLINE | ID: covidwho-1331290

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses innumerous challenges, like understanding what triggered the emergence of this new human virus, how this RNA virus is evolving or how the variability of viral genome may impact the primary structure of proteins that are targets for vaccine. We analyzed 19471 SARS-CoV-2 genomes available at the GISAID database from all over the world and 3335 genomes of other Coronoviridae family members available at GenBank, collecting SARS-CoV-2 high-quality genomes and distinct Coronoviridae family genomes. Additionally, we analyzed 199,984 spike glycoprotein sequences. Here, we identify a SARS-CoV-2 emerging cluster containing 13 closely related genomes isolated from bat and pangolin that showed evidence of recombination, which may have contributed to the emergence of SARS-CoV-2. The analyzed SARS-CoV-2 genomes presented 9632 single nucleotide variants (SNVs) corresponding to a variant density of 0.3 over the genome, and a clear geographic distribution. SNVs are unevenly distributed throughout the genome and hotspots for mutations were found for the spike gene and ORF 1ab. We describe a set of predicted spike protein epitopes whose variability is negligible. Additionally, all predicted epitopes for the structural E, M and N proteins are highly conserved. The amino acid changes present in the spike glycoprotein of variables of concern (VOCs) comprise between 3.4% and 20.7% of the predicted epitopes of this protein. These results favors the continuous efficacy of the available vaccines targeting the spike protein, and other structural proteins. Multiple epitopes vaccines should sustain vaccine efficacy since at least some of the epitopes present in variability regions of VOCs are conserved and thus recognizable by antibodies.


Subject(s)
COVID-19/virology , Pandemics , SARS-CoV-2 , Animals , COVID-19/epidemiology , Databases, Genetic , Genome, Viral , Humans , Mutation , Phylogeography , SARS-CoV-2/classification , SARS-CoV-2/genetics
10.
Genes (Basel) ; 12(7)2021 06 25.
Article in English | MEDLINE | ID: covidwho-1288842

ABSTRACT

A signal analysis of the complete genome sequenced for coronavirus variants of concern-B.1.1.7 (Alpha), B.1.135 (Beta) and P1 (Gamma)-and coronavirus variants of interest-B.1.429-B.1.427 (Epsilon) and B.1.525 (Eta)-is presented using open GISAID data. We deal with a certain new type of finite alternating sum series having independently distributed terms associated with binary (0,1) indicators for the nucleotide bases. Our method provides additional information to conventional similarity comparisons via alignment methods and Fourier Power Spectrum approaches. It leads to uncover distinctive patterns regarding the intrinsic data organization of complete genomics sequences according to its progression along the nucleotide bases position. The present new method could be useful for the bioinformatics surveillance and dynamics of coronavirus genome variants.


Subject(s)
Computational Biology/methods , Genome, Viral , SARS-CoV-2/genetics , Viral Proteins/genetics , Coronavirus/genetics , Humans , SARS-CoV-2/isolation & purification
11.
Mol Biol Evol ; 38(6): 2547-2565, 2021 05 19.
Article in English | MEDLINE | ID: covidwho-1238217

ABSTRACT

Effective systems for the analysis of molecular data are fundamental for monitoring the spread of infectious diseases and studying pathogen evolution. The rapid identification of emerging viral strains, and/or genetic variants potentially associated with novel phenotypic features is one of the most important objectives of genomic surveillance of human pathogens and represents one of the first lines of defense for the control of their spread. During the COVID 19 pandemic, several taxonomic frameworks have been proposed for the classification of SARS-Cov-2 isolates. These systems, which are typically based on phylogenetic approaches, represent essential tools for epidemiological studies as well as contributing to the study of the origin of the outbreak. Here, we propose an alternative, reproducible, and transparent phenetic method to study changes in SARS-CoV-2 genomic diversity over time. We suggest that our approach can complement other systems and facilitate the identification of biologically relevant variants in the viral genome. To demonstrate the validity of our approach, we present comparative genomic analyses of more than 175,000 genomes. Our method delineates 22 distinct SARS-CoV-2 haplogroups, which, based on the distribution of high-frequency genetic variants, fall into four major macrohaplogroups. We highlight biased spatiotemporal distributions of SARS-CoV-2 genetic profiles and show that seven of the 22 haplogroups (and of all of the four haplogroup clusters) showed a broad geographic distribution within China by the time the outbreak was widely recognized-suggesting early emergence and widespread cryptic circulation of the virus well before its isolation in January 2020. General patterns of genomic variability are remarkably similar within all major SARS-CoV-2 haplogroups, with UTRs consistently exhibiting the greatest variability, with s2m, a conserved secondary structure element of unknown function in the 3'-UTR of the viral genome showing evidence of a functional shift. Although several polymorphic sites that are specific to one or more haplogroups were predicted to be under positive or negative selection, overall our analyses suggest that the emergence of novel types is unlikely to be driven by convergent evolution and independent fixation of advantageous substitutions, or by selection of recombined strains. In the absence of extensive clinical metadata for most available genome sequences, and in the context of extensive geographic and temporal biases in the sampling, many questions regarding the evolution and clinical characteristics of SARS-CoV-2 isolates remain open. However, our data indicate that the approach outlined here can be usefully employed in the identification of candidate SARS-CoV-2 genetic variants of clinical and epidemiological importance.


Subject(s)
COVID-19/genetics , Evolution, Molecular , Genome, Viral , Genomics , Phylogeny , SARS-CoV-2/genetics , Humans
12.
Bioessays ; 43(5): e2000325, 2021 05.
Article in English | MEDLINE | ID: covidwho-1191249

ABSTRACT

The origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the subject of many hypotheses. One of them, proposed by Segreto and Deigin, assumes artificial chimeric construction of SARS-CoV-2 from a backbone of RaTG13-like CoV and receptor binding domain (RBD) of a pangolin MP789-like CoV, followed by serial cell or animal passage. Here we show that this hypothesis relies on incorrect or weak assumptions, and does not agree with the results of comparative genomics analysis. The genetic divergence between SARS-CoV-2 and both its proposed ancestors is too high to have accumulated in a lab, given the timeframe of several years. Furthermore, comparative analysis of S-protein gene sequences suggests that the RBD of SARS-CoV-2 probably represents an ancestral non-recombinant variant. These and other arguments significantly weaken the hypothesis of a laboratory origin for SARS-CoV-2, while the hypothesis of a natural origin is consistent with all available genetic and experimental data.


Subject(s)
COVID-19 , Chiroptera , Animals , Humans , Laboratories , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
13.
Heliyon ; 7(3): e06564, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1141868

ABSTRACT

The mortality rates due to COVID-19 have been found disproportionate globally and are currently being researched. India mortality rate with a population of 1.3 billion people is relatively lowest to other countries with high infection rates. Genetic composition of circulating isolates continues to be a key determinant of virulence and pathogenesis. This study aimed to analyse the extent of divergence between genomes of Indian isolates (n = 2525 as compared to reference Wuhan-1 strain and isolates from countries showing higher fatality rates including France, Italy, Belgium, and the USA. The study also analyses the impact of key mutations on interactions with angiotensin converting enzyme 2 (ACE2) and panel of neutralizing monoclonal antibodies. Using 1,44,605 spike protein sequences, global prevalence of mutations in spike protein was observed. The study suggests that SARS-CoV-2 genomes from India share consensus with global trends with respect to D614G as most prevalent mutational event (81.66% among 2525 Indian isolates). Indian isolates did not reported prevalence of N439K mutation in receptor binding motif (RBM) as compared to global isolates (0.54%). Computational docking and molecular dynamics simulation analysis of N439K mutation with respect to ACE 2 binding and reactivity with RBM targeted antibodies viz., B38, BD23, CB6, P2B-F26 and EY6A suggests that variant have relatively higher affinity with ACE 2 receptor which may support higher infectivity. The study warrants large scale monitoring of Indian isolates as SARS-CoV-2 virus is expected to evolve and mutations may appear in unpredictable way.

14.
mSystems ; 6(1)2021 Feb 23.
Article in English | MEDLINE | ID: covidwho-1099746

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in 92 million cases in a span of 1 year. The study focuses on understanding population-specific variations attributing its high rate of infections in specific geographical regions particularly in the United States. Rigorous phylogenomic network analysis of complete SARS-CoV-2 genomes (245) inferred five central clades named a (ancestral), b, c, d, and e (subtypes e1 and e2). Clade d and subclade e2 were found exclusively comprised of U.S. strains. Clades were distinguished by 10 co-mutational combinations in Nsp3, ORF8, Nsp13, S, Nsp12, Nsp2, and Nsp6. Our analysis revealed that only 67.46% of single nucleotide polymorphism (SNP) mutations were at the amino acid level. T1103P mutation in Nsp3 was predicted to increase protein stability in 238 strains except for 6 strains which were marked as ancestral type, whereas co-mutation (P409L and Y446C) in Nsp13 were found in 64 genomes from the United States highlighting its 100% co-occurrence. Docking highlighted mutation (D614G) caused reduction in binding of spike proteins with angiotensin-converting enzyme 2 (ACE2), but it also showed better interaction with the TMPRSS2 receptor contributing to high transmissibility among U.S. strains. We also found host proteins, MYO5A, MYO5B, and MYO5C, that had maximum interaction with viral proteins (nucleocapsid [N], spike [S], and membrane [M] proteins). Thus, blocking the internalization pathway by inhibiting MYO5 proteins which could be an effective target for coronavirus disease 2019 (COVID-19) treatment. The functional annotations of the host-pathogen interaction (HPI) network were found to be closely associated with hypoxia and thrombotic conditions, confirming the vulnerability and severity of infection. We also screened CpG islands in Nsp1 and N conferring the ability of SARS-CoV-2 to enter and trigger zinc antiviral protein (ZAP) activity inside the host cell.IMPORTANCE In the current study, we presented a global view of mutational pattern observed in SARS-CoV-2 virus transmission. This provided a who-infect-whom geographical model since the early pandemic. This is hitherto the most comprehensive comparative genomics analysis of full-length genomes for co-mutations at different geographical regions especially in U.S. strains. Compositional structural biology results suggested that mutations have a balance of opposing forces affecting pathogenicity suggesting that only a few mutations are effective at the translation level. Novel HPI analysis and CpG predictions elucidate the proof of concept of hypoxia and thrombotic conditions in several patients. Thus, the current study focuses the understanding of population-specific variations attributing a high rate of SARS-CoV-2 infections in specific geographical regions which may eventually be vital for the most severely affected countries and regions for sharp development of custom-made vindication strategies.

15.
Gene Rep ; 23: 101020, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1051645

ABSTRACT

Simple sequence repeats (SSRs) or, Microsatellites are short repeat sequences that have been extensively studied in eukaryotic (plants) and prokaryotic (bacteria) organisms. Compared to other organisms, the presence and incidence of SSR on viral genomes are less studied. With the emergence of novel infectious viruses over the past few decades, it is imperative to study the genetic diversity in such viruses to predict their evolutionary and functional changes over time. Following the emergence of SARS-CoV-2, we have assembled 121 complete genomes reported from 31 countries across the six continents for the identification and characterization of SSR repeats. Using two independent SSR identification tools, we have found remarkable consistency in the diversity of microsatellites pattern (38-42 per genome) found in the 121 analyzed SARS-CoV-2 genomes indication their important role for genome stability. Among the identified motifs, trinucleotide and hexanucleotide repeats were found to be the most abundant form followed by mono- and di-nucleotide. There were no tetra- or penta-nucleotide repeats in the analyzed SARS-CoV-2 genomes. The discovery of microsatellites in SARS-CoV-2 genomes may become useful for the population genetics, evolutionary analysis, strain identification and genetic variation.

16.
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
17.
OMICS ; 24(11): 634-644, 2020 11.
Article in English | MEDLINE | ID: covidwho-780306

ABSTRACT

In the first quarter of the 21st century, we are already facing the third emergence of a coronavirus outbreak, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the coronavirus disease 2019 (COVID-19) pandemic. Comparative genomics can inform a deeper understanding of the pathogenesis of COVID-19. Previous strains of coronavirus, SARS-CoV, and Middle-East respiratory syndrome-coronavirus (MERS-CoV), have been known to cause acute lung injuries in humans. SARS-CoV-2 shares genetic similarity with SARS-CoV with some modification in the S protein leading to their enhanced binding affinity toward the angiotensin-converting enzyme 2 (ACE2) receptors of human lung cells. This expert review examines the features of all three coronaviruses through a conceptual lens of comparative genomics. In particular, the life cycle of SARS-CoV-2 that enables its survival within the host is highlighted. Susceptibility of humans to coronavirus outbreaks in the 21st century calls for comparisons of the transmission history, hosts, reservoirs, and fatality rates of these viruses so that evidence-based and effective planetary health interventions can be devised to prevent future zoonotic outbreaks. Comparative genomics offers new insights on putative and novel viral targets with an eye to both therapeutic innovation and prevention. We conclude the expert review by (1) articulating the lessons learned so far, whereas the research is still being actively sought after in the field, and (2) the challenges and prospects in deciphering the linkages among multiomics biological variability and COVID-19 pathogenesis.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Genomics/methods , Pandemics , Pneumonia, Viral/epidemiology , Severe Acute Respiratory Syndrome/epidemiology , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/genetics , COVID-19 , Chiroptera/virology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Eutheria/virology , Global Health/trends , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Protein Binding , Receptors, Virus/genetics , Receptors, Virus/metabolism , /pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/virology , Severity of Illness Index , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Survival Analysis
18.
Proc Natl Acad Sci U S A ; 117(36): 22311-22322, 2020 09 08.
Article in English | MEDLINE | ID: covidwho-724266

ABSTRACT

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike protein. Only mammals fell into the medium to very high categories and only catarrhine primates into the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 spike protein binding and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (frequency <0.001) variants in 10/25 binding sites. In addition, we found significant signals of selection and accelerated evolution in the ACE2 coding sequence across all mammals, and specific to the bat lineage. Our results, if confirmed by additional experimental data, may lead to the identification of intermediate host species for SARS-CoV-2, guide the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/metabolism , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/metabolism , Amino Acids , Animals , Betacoronavirus/metabolism , Binding Sites , COVID-19 , Coronavirus Infections/virology , Evolution, Molecular , Genetic Variation , Host Specificity , Humans , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/virology , Protein Binding , Receptors, Virus/chemistry , Receptors, Virus/genetics , Receptors, Virus/metabolism , SARS-CoV-2 , Selection, Genetic , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Vertebrates
19.
Inflamm Regen ; 40: 17, 2020.
Article in English | MEDLINE | ID: covidwho-706440

ABSTRACT

Coronavirus disease of 2019 (COVID-19), which originated in China in 2019, shows mild cold and pneumonia symptoms that can occasionally worsen and result in deaths. SARS-CoV-2 was reported to be the causative agent of the disease and was identified as being similar to SARS-CoV, a causative agent of SARS in 2003. In this review, we described the phylogeny of SARS-CoV-2, covering various related studies, in particular, focusing on viruses obtained from horseshoe bats and pangolins that belong to Sarbecovirus, a subgenus of Betacoronavirus. We also describe the virological characteristics of SARS-CoV-2 and compare them with other coronaviruses. More than 30,000 genome sequences of SARS-CoV-2 are available in the GISAID database as of May 28, 2020. Using the genome sequence data of closely related viruses, the genomic characteristics and evolution of SARS-CoV-2 were extensively studied. However, given the global prevalence of COVID-19 and the large number of associated deaths, further computational and experimental virological analyses are required to fully characterize SARS-CoV-2.

20.
Biochim Biophys Acta Mol Basis Dis ; 1866(10): 165878, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-597413

ABSTRACT

The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective.


Subject(s)
Betacoronavirus/genetics , Genome, Viral , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cytokines/metabolism , Genetic Variation , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , RNA-Dependent RNA Polymerase/genetics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry
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