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Atomistic simulation reveals structural mechanisms underlying D614G spike glycoprotein‐enhanced fitness in SARS‐COV ‐2
Author(s) -
Omotuyi I. Olaposi,
Nash Oyekanmi,
Ajiboye O. Basiru,
Iwegbulam C. Gift,
Oyinloye E. Babatunji,
Oyedeji O. Abimbola,
Kashim Z. Abimbola,
Okaiyeto Kunle
Publication year - 2020
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.26383
Subject(s) - mutant , glycoprotein , receptor , wild type , plasma protein binding , chemistry , coronavirus , biology , microbiology and biotechnology , biochemistry , covid-19 , gene , medicine , disease , pathology , infectious disease (medical specialty)
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.