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

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dc.creatorUl Alam, Rubayet A. S. M.
dc.creatorIslam, Ovinu Kibria
dc.creatorHasan, Md. Shazid
dc.creatorIslam, Mir Raihanul
dc.creatorMahmud, Shafi
dc.creatorAl-Emran, Hassan M.
dc.creatorJahid, Iqbal Kabir
dc.creatorCrandall, Keith A.
dc.creatorHossain, M. Anwar
dc.date2022-03
dc.date2024-04-12T13:37:41Z
dc.date2024-04-12T13:37:41Z
dc.date.accessioned2026-06-27T15:30:41Z
dc.descriptionSevere 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 G614 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.
dc.identifierhttps://hdl.handle.net/10568/141321
dc.identifier.urihttp://hdl.handle.net/123456789/106519
dc.languageen
dc.publisherWiley
dc.rightsOpen Access
dc.sourceRubayet Ul Alam, A. S. M.; Islam, Ovinu Kibria; Hasan, Md. Shazid; Islam, Mir Raihanul; Mahmud, Shafi; Al-Emran, Hassan M.; Jahid, Iqbal Kabir; Crandall, Keith A.; and Hossain, M. Anwar. 2022. Dominant clade-featured SARS-CoV-2 co-occurring mutations reveals plausible epistasis: An in silico based hypothetical model. Journal of Medical Virology. Journal of Medical Virology 94(3): 1035-1049. https://doi.org/10.1002/jmv.27416
dc.subjectmodels
dc.subjectviruses
dc.subjectcovid-19
dc.subjectmutation
dc.subjectpathogenicity
dc.subjectvirulence
dc.subjectclades
dc.titleDominant clade-featured SARS-CoV-2 co-occurring mutations reveals plausible epistasis: An in silico based hypothetical model
dc.typeJournal Article

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