Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Genome Wide Analysis of Severe Acute Respiratory Syndrome Coronavirus-2 Implicates World-Wide Circulatory Virus Strains Heterogeneity

Version 1 : Received: 8 April 2020 / Approved: 9 April 2020 / Online: 9 April 2020 (05:56:35 CEST)

How to cite: Islam, M.R.; Hoque, M.N.; Rahman, M.S.; Puspo, J.A.; Akhter, M.; Akter, S.; Rubayet-Ul-Alam, A.S.M.; Sultana, M.; Crandall, K.A.; Hossain, M.A. Genome Wide Analysis of Severe Acute Respiratory Syndrome Coronavirus-2 Implicates World-Wide Circulatory Virus Strains Heterogeneity. Preprints 2020, 2020040137 (doi: 10.20944/preprints202004.0137.v1). Islam, M.R.; Hoque, M.N.; Rahman, M.S.; Puspo, J.A.; Akhter, M.; Akter, S.; Rubayet-Ul-Alam, A.S.M.; Sultana, M.; Crandall, K.A.; Hossain, M.A. Genome Wide Analysis of Severe Acute Respiratory Syndrome Coronavirus-2 Implicates World-Wide Circulatory Virus Strains Heterogeneity. Preprints 2020, 2020040137 (doi: 10.20944/preprints202004.0137.v1).

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel evolutionarily divergent RNA virus etiological agent of COVID-19, is responsible for present devastating pandemic respiratory illness. To explore the genomic signatures, we comprehensively analyzed 2,492 complete and/or near-complete genome sequences of SARS-CoV-2 strains reported from across the globe to the GISAID database up to 30 March 2020. Genome-wide annotations revealed 1,407 nucleotide-level mutations at different positions throughout the entire genome of SARS-CoV-2. Moreover, nucleotide deletion analysis found nine deletions throughout the genome, including in polyprotein (n=6), ORF10 (n=1) and 3´-UTR (n=2). Evidence from the systematic gene-level mutational and protein profile analyses revealed a large number of amino acid (aa) substitutions (n=722), making the viral proteins heterogeneous. Notably, residues of receptor-binding domain (RBD) having crucial interactions with angiotensin-converting enzyme 2 (ACE2), and cross-reacting neutralizing antibody were found to be conserved among the analyzed SARS-CoV-2 strains, except for replacement of Lysine with Arginine at 378 position of the cryptic epitope of a Shanghai isolate, hCoV-19/Shanghai/SH0007/2020 (EPI_ISL_416320). Our method of genome annotation is a promising tool for monitoring and tracking the epidemic, the associated genetic variants, and their implications for the development of effective control and prophylaxis strategy.

Subject Areas

SARS-CoV-2; genomes; nucleotide; amino-acid; mutations; replacements

Comments (2)

Comment 1
Received: 10 April 2020
Commenter: Jiang
The commenter has declared there is no conflict of interests.
Comment: Is it possible that the observed mutations in RNA viruses are caused by RNA modification by the host? Such as C-to-U deamination. How would this impact your analyses?
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Response 1 to Comment 1
Received: 14 April 2020
Commenter: M. Anwar Hossain, PhD
The commenter has declared there is no conflict of interests.
Comment: Thank you Mr. Jiang for nice comment. Mutation on RNA virus genome is influenced by several factors including both virus genomic composition and host-factors. The frequently observed mutations in RNA virus genome are modulated by polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post-replicative repair (Sanjuán & Domingo-Calap, 2016; doi: 10.1007/s00018-016-2299-6). Most exciting unresolved questions regarding RNA virus mutation include unveiling the interplays between mutation and recombination, the roles played by viral accessory proteins in determining mutation rates, the effects of host-encoding enzymes (cytidine/adenine deaminases) on viral diversity and evolution (Duffy, 2018; https://doi.org/10.1371/journal.pbio.3000003), whether mutation accumulation can be evolutionary adjusted by modifying viral replication modes, and how template sequences regulate viral mutation rates (Sanjuán & Domingo-Calap, 2016; doi: 10.1007/s00018-016-2299-6). Furthermore, RNA virus mutation rates vary across different host cells (Combe & Sanjuan, 2014; doi: 10.1371/journal.ppat.1003855). Our current analyses highlight the deletion mutations and amino acid substitutions of SARS-CoV-2, an emerging RNA virus causing the ongoing COVID-19 pandemic. The viral genetic diversity may result from multiple virus- and host-dependent processes above-mentioned. Most importantly, viral mutation rates can evolve in response to specific selective pressures that need further in depth studies to point out specifically.

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