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 (M pro ) 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.
【저자키워드】 Coronavirus disease 2019, severe acute respiratory syndrome coronavirus-2, SARS-CoV-2 mutations, single amino acid substitutions, SARS-CoV-2 pathogenesis, 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, coronavirus, Mutation, Pathogenesis, S protein, Variation, Infection, severe acute respiratory syndrome coronavirus-2, protease, severe acute respiratory syndrome Coronavirus, Replication, Surface glycoprotein, Severe acute respiratory syndrome, Protein, Health, nucleocapsid, Comparative genomics, Therapeutic strategies, RdRP, RNA-dependent RNA polymerase, envelope, membrane, structural proteins, small molecule, structural protein, respiratory, Enzymes, mechanism, association, Coronavirus-2, Analysis, Structural variation, (RdRp, acute respiratory syndrome, acute respiratory syndrome coronavirus, failure, therapeutic approaches, M pro, acute respiratory syndrome coronavirus-2, sequence, structural variations, Affect, structure-function, selected, performed, mutated, rising, creating, functional consequence, 【제목키워드】 SARS-CoV-2, Genomics, Impact, Comparative,