Dominant clade-featured SARS-CoV-2 co-occurring mutations reveal plausible epistasis: An in silico based hypothetical model.

Autor: Alam ASMRU; Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh., Islam OK; Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh., Hasan MS; Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh., Islam MR; Division of Poverty, Health, and Nutrition, International Food Policy Research Institute, Bangladesh., Mahmud S; Department Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, Bangladesh., Al-Emran HM; Department of Biomedical Engineering, Jashore University of Science and Technology, Jashore, Bangladesh., Jahid IK; Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh., Crandall KA; Department of Biostatistics and Bioinformatics, Computational Biology Institute, Milken Institute School of Public Health, The George Washington University, Washington DC, USA., Hossain MA; Office of the Vice Chancellor, Jashore University of Science and Technology, Jashore, Bangladesh.; Department of Microbiology, University of Dhaka, Dhaka, Bangladesh.
Jazyk: angličtina
Zdroj: Journal of medical virology [J Med Virol] 2022 Mar; Vol. 94 (3), pp. 1035-1049. Date of Electronic Publication: 2021 Nov 01.
DOI: 10.1002/jmv.27416
Abstrakt: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into eight fundamental clades with four of these clades (G, GH, GR, and GV) globally prevalent in 2020. To explain plausible epistatic effects of the signature co-occurring mutations of these circulating clades on viral replication and transmission fitness, we proposed a hypothetical model using in silico approach. Molecular docking and dynamics analyses showed the higher infectiousness of a spike mutant through more favorable binding of G 614 with the elastase-2. RdRp mutation p.P323L significantly increased genome-wide mutations (p < 0.0001), allowing for more flexible RdRp (mutated)-NSP8 interaction that may accelerate replication. Superior RNA stability and structural variation at NSP3:C241T might impact protein, RNA interactions, or both. Another silent 5'-UTR:C241T mutation might affect translational efficiency and viral packaging. These four G-clade-featured co-occurring mutations might increase viral replication. Sentinel GH-clade ORF3a:p.Q57H variants constricted the ion-channel through intertransmembrane-domain interaction of cysteine(C81)-histidine(H57). The GR-clade N:p.RG203-204KR would stabilize RNA interaction by a more flexible and hypo-phosphorylated SR-rich region. GV-clade viruses seemingly gained the evolutionary advantage of the confounding factors; nevertheless, N:p.A220V might modulate RNA binding with no phenotypic effect. Our hypothetical model needs further retrospective and prospective studies to understand detailed molecular events and their relationship to the fitness of SARS-CoV-2.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: