Genomic Variations in the Structural Proteins of SARS-CoV-2 and Their Deleterious Impact on Pathogenesis: A Comparative Genomics Approach.
A continual rise in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease (COVID-19) has become a global threat. The main problem comes when SARS-CoV-2 gets mutated with the rising infection and becomes more lethal for humankind than ever. Mutations in the structural proteins of SARS-CoV-2, i.e., the spike surface glycoprotein (S), envelope (E), membrane (M) and nucleocapsid (N), and replication machinery enzymes, i.e., main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) creating more complexities towards pathogenesis and the available COVID-19 therapeutic strategies. This study analyzes how a minimal variation in these enzymes, especially in S protein at the genomic/proteomic level, affects pathogenesis. The structural variations are discussed in light of the failure of small molecule development in COVID-19 therapeutic strategies. We have performed in-depth sequence- and structure-based analyses of these proteins to get deeper insights into the mechanism of pathogenesis, structure-function relationships, and development of modern therapeutic approaches. Structural and functional consequences of the selected mutations on these proteins and their association with SARS-CoV-2 virulency and human health are discussed in detail in the light of our comparative genomics analysis.
['Mohammad|Taj|T|', 'Choudhury|Arunabh|A|', 'Habib|Insan|I|', 'Asrani|Purva|P|', 'Mathur|Yash|Y|', 'Umair|Mohd|M|', 'Anjum|Farah|F|', 'Shafie|Alaa|A|', 'Yadav|Dharmendra Kumar|DK|', 'Hassan|Md Imtaiyaz|MI|']
D000086382:COVID-19 D023281:Genomics D006801:Humans D040901:Proteomics D000086402:SARS-CoV-2 D064370:Spike Glycoprotein, Coronavirus
severe acute respiratory syndrome coronavirus-2 SARS-CoV-2 mutations SARS-CoV-2 pathogenesis coronavirus disease 2019 single amino acid substitutions