Genome-wide analysis of SARS-CoV-2 virus strains circulating worldwide implicates heterogeneity

Islam, M. Rafiul; Hoque, M. Nazmul; Rahman, M. Shaminur; Alam, A. S. M. Rubayet Ul; Akther, Masuda; Puspo, J. Akter; Akter, Salma; Sultana, Munawar; Crandall, Keith A.; Hossain, M. Anwar

doi:10.1038/s41598-020-70812-6

Cited by 267 publications

(319 citation statements)

References 40 publications

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“…To this regard, we note that the two common endemic human coronaviruses, HCoV-OC43 [33] and HCoV-299E [34], have extensive deletions in the C-terminal region of nsp1. Thought crystallization and biological data are needed to confirm our hypothesis, our observations, together with the recent findings of two viral strains carrying in one case an extensive deletion in the orf7a gene [35], a deletion in the nsp2 gene [36] and deletions in nsp1 gene also identified by other groups [37,38], indicate that SARS-CoV-2 genome may be undergoing a significant evolutionary process, which may result in virushost adaptation [39]. Since the overwhelming majority of genomic sequences collected so far are from symptomatic subjects, it seems logical to characterize in detail SARS-CoV-2 genomes from the asymptomatic population.…”

Section: Discussionsupporting

confidence: 82%

Emerging of a SARS-CoV-2 viral strain with a deletion in nsp1

et al. 2020

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Background: The new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first detected in Wuhan (China) in December of 2019 is responsible for the current global pandemic. Phylogenetic analysis revealed that it is similar to other betacoronaviruses, such as SARS-CoV and Middle-Eastern Respiratory Syndrome, MERS-CoV. Its genome is ∼ 30 kb in length and contains two large overlapping polyproteins, ORF1a and ORF1ab that encode for several structural and non-structural proteins. The non-structural protein 1 (nsp1) is arguably the most important pathogenic determinant, and previous studies on SARS-CoV indicate that it is both involved in viral replication and hampering the innate immune system response. Detailed experiments of site-specific mutagenesis and in vitro reconstitution studies determined that the mechanisms of action are mediated by (a) the presence of specific amino acid residues of nsp1 and (b) the interaction between the protein and the host's small ribosomal unit. In fact, substitution of certain amino acids resulted in reduction of its negative effects. Methods: A total of 17,928 genome sequences were obtained from the GISAID database (December 2019 to July 2020) from patients infected by SARS-CoV-2 from different areas around the world. Genomes alignment was performed using MAFFT (REFF) and the nsp1 genomic regions were identified using BioEdit and verified using BLAST. Nsp1 protein of SARS-CoV-2 with and without deletion have been subsequently modelled using I-TASSER. Results: We identified SARS-CoV-2 genome sequences, from several Countries, carrying a previously unknown deletion of 9 nucleotides in position 686-694, corresponding to the AA position 241-243 (KSF). This deletion was found in different geographical areas. Structural prediction modelling suggests an effect on the C-terminal tail structure. Conclusions: Modelling analysis of a newly identified deletion of 3 amino acids (KSF) of SARS-CoV-2 nsp1 suggests that this deletion could affect the structure of the C-terminal region of the protein, important for regulation of viral replication and negative effect on host's gene expression. In addition, substitution of the two amino acids (KS) from nsp1 of SARS-CoV was previously reported to revert loss of interferon-alpha expression. The deletion that we describe indicates that SARS-CoV-2 is undergoing profound genomic changes. It is important to: (i) confirm the spreading of this particular viral strain, and potentially of strains with other deletions in the nsp1 protein, both in the population of asymptomatic and pauci-symptomatic subjects, and (ii) correlate these changes in nsp1 with potential decreased viral pathogenicity.

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Section: Discussionsupporting

confidence: 82%

Emerging of a SARS-CoV-2 viral strain with a deletion in nsp1

et al. 2020

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“…Approximately, 30 kilobase sized genome of the novel SARS-CoV-2 encodes several smaller open reading frames (ORFs) (Rota et al, 2003;Freundt et al, 2010, Cotten et al, 2013. These ORFs encode for different proteins for example the replicase polyprotein, the spike (S) glycoprotein, envelope (E), membrane (M), nucleocapsid (N) proteins, accessory proteins, and other non-structural proteins (nsp) (Ahmed, Quadeer & McKay, 2020;Islam et al, 2020;Phan, 2020;Walls et al, 2020). The genome of SARS-CoV-2 coupled with regions of genomic instability (Abdelmageed et al, 2020;Rahman et al, 2020), which encodes for multiple structural and non-structural proteins (Ahmed, Quadeer & McKay, 2020;Rahman et al, 2020) with many unique features.…”

Section: Introductionmentioning

confidence: 99%

“…The genome of SARS-CoV-2 coupled with regions of genomic instability (Abdelmageed et al, 2020;Rahman et al, 2020), which encodes for multiple structural and non-structural proteins (Ahmed, Quadeer & McKay, 2020;Rahman et al, 2020) with many unique features. These features make these proteins prone to frequent coding changes, thus generating new strains in a short period of time (Hemida & Abduallah, 2020;Islam et al, 2020). Rapid mutational frequencies are associated with the poor proofreading efficiency of the viral RNA polymerase, and the likelihood of recombination between different members of this family (Jackwood, Hall & Handel, 2012;Phan, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…The relatively faster spread and varying levels of fatality of SARS-CoV-2 in different countries raises an intriguing question whether the evolution of this virus is driven by mutations. To address these question, several recent studies reported that substitution and/or deletion of nucleotides and amino acids (aa) at the entire genome of SARS-CoV-2 are the important mechanisms for virus evolution in nature (Huang et al, 2020;Islam et al, 2020;Phan, 2020;Yin, 2020). Due to the practice of open science, the research progress on SARS-CoV-2 is the fastest moving subject in the human history.…”

Section: Introductionmentioning

confidence: 99%

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Genomic diversity and evolution, diagnosis, prevention, and therapeutics of the pandemic COVID-19 disease

Hoque

Chaudhury

Akanda

et al. 2020

PeerJ

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The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by a novel evolutionarily divergent RNA virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus first emerged in Wuhan, China in December 2019, and subsequently spreaded around the world. Genomic analyses revealed that this zoonotic virus may be evolved naturally but not a purposefully manipulated laboratory construct. However, currently available data are not sufficient to precisely conclude the origin of this fearsome virus. Comprehensive annotations of the whole-genomes revealed hundreds of nucleotides, and amino acids mutations, substitutions and/or deletions at different positions of the ever changing SARS-CoV-2 genome. The spike (S) glycoprotein of SARS-CoV-2 possesses a functional polybasic (furin) cleavage site at the S1-S2 boundary through the insertion of 12 nucleotides. It leads to the predicted acquisition of 3-O-linked glycan around the cleavage site. Although real-time RT-PCR methods targeting specific gene(s) have widely been used to diagnose the COVID-19 patients, however, recently developed more convenient, cheap, rapid, and specific diagnostic tools targeting antigens or CRISPR-Cas-mediated method or a newly developed plug and play method should be available for the resource-poor developing countries. A large number of candidate drugs, vaccines and therapies have shown great promise in early trials, however, these candidates of preventive or therapeutic agents have to pass a long path of trials before being released for the practical application against COVID-19. This review updates current knowledge on origin, genomic evolution, development of the diagnostic tools, and the preventive or therapeutic remedies of the COVID-19. We also discussed the future scopes for research, effective management, and surveillance of the newly emerged COVID-19 disease.

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“…This may contribute to understand the pathogenic dynamics of the virus over time. The genetic differences among SARS-CoV-2 strains from different location can be linked with their geographical distributions (12). The recent studies suggested that dry and cold climate can boost the spreading of the infections (13).…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of SARS-CoV-2 from Bangladesh: Implications in genetic diversity, possible origin of the virus, and functional significance of the mutations

Rahman

Kader

Rizvi

2020

Preprint

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In a try to understand the pathogenesis, evolution, and epidemiology of the SARS-CoV-2 virus, scientists from all over the world are tracking its genomic changes in real-time. Genomic studies can be helpful in understanding the disease dynamics. We have downloaded 324 complete and near-complete SARS-CoV-2 genomes submitted in the GISAID database from Bangladesh which were isolated between 30 March to 7 September 2020. We then compared these genomes with the Wuhan reference sequence and found 4160 mutation events including 2253 missense single nucleotide variations, 38 deletions, and 10 insertions. The C>T nucleotide change was most prevalent possibly due to selective mutation pressure to reduce CpG sites to evade CpG targeted host immune response. The most frequent mutation that occurred in 98% of the isolates was 3037C>T which is a synonymous change that almost always accompanied 3 other mutations that include 241C>T, 14408C>T (P323L in RdRp), and 23403A>G (D614G in spike protein). The P323L was reported to increase mutation rate and D614G is associated with increased viral replication and currently the most prevalent variant circulating all over the world. We identified multiple missense mutations in B-cell and T-cell predicted epitope regions and/or PCR target regions (including R203K and G204R that occurred in 86% of the isolates) that may impact immunogenicity and/or RT-PCR based diagnosis. Our analysis revealed 5 large deletion events in ORF7a and ORF8 gene products that may be associated with less severity of the disease and increased viral clearance. Our phylogeny analysis identified most of the isolates belonged to the Nextstrain clade 20B (86%) and GISAID clade GR (88%). Most of our isolates shared common ancestors either directly with European countries or jointly with middle eastern countries as well as Australia and India. Interestingly, the 19B clade (GISAID S clade) was unique to Chittagong which was originally prevalent in China. This reveals possible multiple introductions of the virus in Bangladesh via different routes. Hence more genome sequencing and analysis with related clinical data are needed to interpret the functional significance and better predict the disease dynamics that may be helpful for policymakers to control the COVID-19 pandemic in Bangladesh.

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Genome-wide analysis of SARS-CoV-2 virus strains circulating worldwide implicates heterogeneity

Cited by 267 publications

References 40 publications

Emerging of a SARS-CoV-2 viral strain with a deletion in nsp1

Emerging of a SARS-CoV-2 viral strain with a deletion in nsp1

Genomic diversity and evolution, diagnosis, prevention, and therapeutics of the pandemic COVID-19 disease

Molecular characterization of SARS-CoV-2 from Bangladesh: Implications in genetic diversity, possible origin of the virus, and functional significance of the mutations

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