Atomistic simulation reveals structural mechanisms underlying D614G spike glycoprotein-enhanced fitness in SARS-COV-2

I. Olaposi Omotuyi, Oyekanmi Nash, O. Basiru Ajiboye, C. Gift Iwegbulam, Babatunji Emmanuel Oyinloye, O. Abimbola Oyedeji, Z. Abimbola Kashim, Kunle Okaiyeto

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

7 Citas (Scopus)

Resumen

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.
Idioma originalInglés
PublicaciónJournal of Computational Chemistry
Volumen41
N.º24
DOI
EstadoPublicada - 15 sep 2020

Huella Profundice en los temas de investigación de 'Atomistic simulation reveals structural mechanisms underlying D614G spike glycoprotein-enhanced fitness in SARS-COV-2'. En conjunto forman una huella única.

Citar esto