Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel evolutionary divergent RNA virus, is responsible for the present devastating COVID-19 pandemic. 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 1,516 nucleotide-level variations at different positions throughout the entire genome of SARS-CoV-2. Moreover, nucleotide (nt) deletion analysis found twelve deletion sites throughout the genome other than previously reported deletions at coding sequence of the ORF8 (open reading frame), spike, and ORF7a proteins, specifically in polyprotein ORF1ab (n = 9), 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 = 744), demonstrating the viral proteins heterogeneous. Notably, residues of receptor-binding domain (RBD) showing crucial interactions with angiotensin-converting enzyme 2 (ACE2) and cross-reacting neutralizing antibody were found to be conserved among the analyzed virus strains, except for replacement of lysine with arginine at 378th position of the cryptic epitope of a Shanghai isolate, hCoV-19/Shanghai/SH0007/2020 (EPI_ISL_416320). Furthermore, our results of the preliminary epidemiological data on SARS-CoV-2 infections revealed that frequency of aa mutations were relatively higher in the SARS-CoV-2 genome sequences of Europe (43.07%) followed by Asia (38.09%), and North America (29.64%) while case fatality rates remained higher in the European temperate countries, such as Italy, Spain, Netherlands, France, England and Belgium. Thus, the present method of genome annotation employed at this early pandemic stage could be a promising tool for monitoring and tracking the continuously evolving pandemic situation, the associated genetic variants, and their implications for the development of effective control and prophylaxis strategies.
Highlights
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel evolutionary divergent RNA virus, is responsible for the present devastating COVID-19 pandemic
Nucleotide sequence alignment revealed a total of 1,516 mutations across the entire set of genomes of the SARS-CoV-2 strains compared to the NCBI reference strain, Wuhan-Hu-1 (Accession NC_045512)
The ORF3a, ORF6, ORF7ab, ORF8, and ORF10 had a total of 92, 8, 54, 33 and 17 nucleotide-level variations, respectively whereas 105, 158 and 6-nt mutations were sequentially detected in 5 ́-UTR, 3 ́-UTR, and spacer regions (Supplementary Table 1b)
Summary
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel evolutionary divergent RNA virus, is responsible for the present devastating COVID-19 pandemic. This study has targeted the genome-wide mutational spectra covering nucleotide, aa and deletion mutations in 2,492 complete (and/or near complete) genomes of SARS-CoV-2 retrieved from the global initiative on sharing all influenza data (GISAID) (https://www.gisaid.org/) up to 30 March 2020 (Supplementary Fig. 1, Supplementary Table 1a). These preliminary data of SARS-CoV-2 genome sequences belonged to different geographic and climatic conditions for inference on the evolution of this novel virus
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