Atomistic simulation reveals structural mechanisms underlying D614G spike glycoprotein‐enhanced fitness in SARS‐COV‐2. Issue 24 (21st July 2020)

• Record Type: Journal Article
• Authors: Omotuyi, I. Olaposi; Nash, Oyekanmi; Ajiboye, O. Basiru; Iwegbulam, C. Gift; Oyinloye, E. Babatunji; Oyedeji, O. Abimbola; Kashim, Z. Abimbola; Okaiyeto, Kunle
• Is Part Of: Journal of computational chemistry. Volume 41:Issue 24(2020)
• Page Start: 2158
• Page End: 2161
• Publication Date: 2020-07-21
• Subjects: COVID‐19 -- molecular dynamics simulation -- mutation -- SARS‐COV‐2 -- spike glycoprotein; Chemistry -- Data processing -- Periodicals; 542.85
• DOI: 10.1002/jcc.26383
• Languages: English
• ISSNs: 0192-8651

Abstract

Abstract: D614G spike glycoprotein (sgp) mutation in rapidly spreading severe acute respiratory syndrome coronavirus‐2 (SARS‐COV‐2) is associated with enhanced fitness and higher transmissibility in new cases of COVID‐19 but the underlying mechanism is unknown. Here, using atomistic simulation, a plausible mechanism has been delineated. In G614 sgp but not wild type, increased D(G)614‐T859 Cα‐distance within 65 ns is interpreted as S1/S2 protomer dissociation. Overall, ACE2‐binding, post‐fusion core, open‐state and sub‐optimal antibody‐binding conformations were preferentially sampled by the G614 mutant, but not wild type. Furthermore, in the wild type, only one of the three sgp chains has optimal communication route between residue 614 and the receptor‐binding domain (RBD); whereas, two of the three chains communicated directly in G614 mutant. These data provide evidence that D614G sgp mutant is more available for receptor binding, cellular invasion and reduced antibody interaction; thus, providing framework for enhanced fitness and higher transmissibility in D614G SARS‐COV‐2 mutant. Abstract : The causative agent of COVID‐19; SARS‐COV‐2 has acquired a rare mutation (G23403A) in the region encoding spike glycoprotein (D614G) resulting in enhanced fitness and higher transmissibility. Here, MD simulation has revealed evidence of S1/S2 protomer disaggregation, preferential sampling of post‐fusion, and receptor‐binding (ACE2) conformations and enhanced communication between residue 614 and receptor‐binding domain in D6 mutant; thus, providing structural framework for improved cellular invasion and higher fitness in D614G mutant but not wild type SARS‐COV‐2.