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Comput Biol Med . SARS-CoV-2 NSP14 governs mutational instability and assists in making new SARS-CoV-2 variants

tetano

Editor, Senior Moderator
Comput Biol Med


. 2024 Jan 12:170:107899.
doi: 10.1016/j.compbiomed.2023.107899. Online ahead of print. SARS-CoV-2 NSP14 governs mutational instability and assists in making new SARS-CoV-2 variants

Sk Sarif Hassan[SUP] 1 [/SUP], Tanishta Bhattacharya[SUP] 2 [/SUP], Debaleena Nawn[SUP] 3 [/SUP], Ishana Jha[SUP] 4 [/SUP], Pallab Basu[SUP] 5 [/SUP], Elrashdy M Redwan[SUP] 6 [/SUP], Kenneth Lundstrom[SUP] 7 [/SUP], Debmalya Barh[SUP] 8 [/SUP], Bruno Silva Andrade[SUP] 9 [/SUP], Murtaza M Tambuwala[SUP] 10 [/SUP], Alaa A Aljabali[SUP] 11 [/SUP], Altijana Hromić-Jahjefendić[SUP] 12 [/SUP], Wagner Baetas-da-Cruz[SUP] 13 [/SUP], Ángel Serrano-Aroca[SUP] 14 [/SUP], Vladimir N Uversky[SUP] 15 [/SUP]



Affiliations
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the rapidly evolving RNA virus behind the COVID-19 pandemic, has spawned numerous variants since its 2019 emergence. The multifunctional Nonstructural protein 14 (NSP14) enzyme, possessing exonuclease and messenger RNA (mRNA) capping capabilities, serves as a key player. Notably, single and co-occurring mutations within NSP14 significantly influence replication fidelity and drive variant diversification. This study comprehensively examines 120 co-mutations, 68 unique mutations, and 160 conserved residues across NSP14 homologs, shedding light on their implications for phylogenetic patterns, pathogenicity, and residue interactions. Quantitative physicochemical analysis categorizes 3953 NSP14 variants into three clusters, revealing genetic diversity. This research underscoresthe dynamic nature of SARS-CoV-2 evolution, primarily governed by NSP14 mutations. Understanding these genetic dynamics provides valuable insights for therapeutic and vaccine development.

Keywords: Clustering; Co-mutations-flow; Invariant residues; Nonstructural protein 14 (NSP14); RdRp; SARS-CoV-2.

 
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