Comparative insight into the genomic landscape of SARS-CoV-2 and identification of mutations associated with the origin of infection and diversity

The analyses of 2325 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomes revealed 107, 162, and 65 nucleotide substitutions in the coding region of SARS-CoV-2 from the three continents America, Europe, and Asia, respectively. Of these nucleotide substitutions 58, 94, and 37 were nonsynonymous types mostly present in the Nsp2, Nsp3, Spike, and ORF9. A continent-specific phylogram analyses clustered the SARS-CoV-2 in the different group based on the frequency of nucleotide substitutions. Detailed analyses about the continent-specific amino acid changes and their effectiveness by SNAP2 software was investigated. We found 11 common nonsynonymous mutations; among them, two novel effective mutations were identified in ORF9 (S194L and S202N). Intriguingly, ORF9 encodes nucleocapsid phosphoprotein possessing many effective mutations across continents and could be a potential candidate after the spike protein for studying the role of mutation in viral assembly and pathogenesis. Among the two forms of certain frequent mutation, one form is more prevalent in Europe continents (Nsp12:L314, Nsp13:P504, Nsp13:Y541, Spike:G614, and ORF8:L84) while other forms are more prevalent in American (Nsp12:P314, Nsp13:L504, Nsp13:C541, Spike:D614, and ORF8:L84) and Asian continents (Spike:D614), indicating the spatial and temporal dynamics of SARS-CoV-2. We identified highly conserved 38 regions and among these regions, 11 siRNAs were predicted on stringent criteria that can be used to suppress the expression of viral genes and the corresponding reduction of human viral infections. The present investigation provides information on different mutations and will pave the way for differentiating strains based on virulence and their use in the development of better antiviral therapy.

Automated summary

The study analyzed 2325 SARS-CoV-2 genomes from America, Europe, and Asia, identifying numerous nucleotide substitutions, particularly nonsynonymous, in key coding regions. The nucleotide substitutions, mutation patterns, and phylogenetic analyses revealed continent-specific differences in the virus strains, highlighting the importance of ORF9 and its potential role in viral assembly and pathogenesis. Furthermore, the spatial and temporal dynamics of SARS-CoV-2 mutations across continents were noted, along with the identification of highly conserved regions and potential siRNAs for antiviral therapy development.