Genomic and proteomic mutation landscapes of SARS-CoV-2

Abstract

The ongoing pandemic caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), affects thousands of people every day worldwide. Hence, drugs and vaccines effective against all variants of SARS-CoV-2 are crucial today. Viral genome mutations exist commonly which may impact the encoded proteins, possibly resulting to varied effectivity of detection tools and disease treatment. Thus, this study surveyed the SARS-CoV-2 genome and proteome and evaluated its mutation characteristics. Phylogenetic analyses of SARS-CoV-2 genes and proteins show three major clades and one minor clade (P6810S; ORF1ab). The overall frequency and densities of mutations in the genes and proteins of SARS-CoV-2 were observed. Nucleocapsid exhibited the highest mutation density among the structural proteins while the spike D614G was the most common, occurring mostly in genomes outside China and United States. ORF8 protein had the highest mutation density across all geographical areas. Moreover, mutation hotspots neighboring and at the catalytic site of RNA-dependent RNA polymerase were found that might challenge the binding and effectivity of remdesivir. Mutation coldspots may present as conserved diagnostic and therapeutic targets were found in ORF7b, ORF9b, and ORF14. These findings suggest that the virion's genotype and phenotype in a specific population should be considered in developing diagnostic tools and treatment options.