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Relevant SARS-CoV-2 Genome Variation through Six Months of Worldwide Monitoring.

ABSTRACT: Real-time genome monitoring of the SARS-CoV-2 pandemic outbreak is of utmost importance for designing diagnostic tools, guiding antiviral treatment and vaccination strategies. In this study, we present an accurate method for temporal and geographical comparison of mutational events based on GISAID database genome sequencing. Among 42523 SARS-CoV-2 genomes analyzed, we found 23202 variants compared to the reference genome. The Ti/Tv (transition/transversion) ratio was used to filter out possible false-positive errors. Transition mutations generally occurred more frequently than transversions. Our clustering analysis revealed remarkable hotspot mutation patterns for SARS-CoV-2. Mutations were clustered based on how their frequencies changed over time according to each geographical location. We observed some clusters showing a clear variation in mutation frequency and continuously evolving in the world. However, many mutations appeared in specific periods without a clear pattern over time. Various important nonsynonymous mutations were observed, mainly in Oceania and Asia. More than half of these mutations were observed only once. Four hotspot mutations were found in all geographical locations at least once: T265I (NSP2), P314L (NSP12), D614G (S), and Q57H (ORF3a). The current analysis of SARS-CoV-2 genomes provides valuable information on the geographical and temporal mutational evolution of SARS-CoV-2.

SUBMITTER: Hakmaoui A

PROVIDER: S-EPMC8241501 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.

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Relevant SARS-CoV-2 Genome Variation through Six Months of Worldwide Monitoring.

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