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Population Dynamics and Structural Effects at Short and Long Range Support the Hypothesis of the Selective Advantage of the G614 SARS-CoV-2 Spike Variant.

Authors :
Trucchi, Emiliano
Gratton, Paolo
Mafessoni, Fabrizio
Motta, Stefano
Cicconardi, Francesco
Mancia, Filippo
Bertorelle, Giorgio
D'Annessa, Ilda
Marino, Daniele Di
Source :
Molecular Biology & Evolution; May2021, Vol. 38 Issue 5, p1966-1979, 14p
Publication Year :
2021

Abstract

SARS-CoV-2 epidemics quickly propagated worldwide, sorting virus genomic variants in newly established propagules of infections. Stochasticity in transmission within and between countries or an actual selective advantage could explain the global high frequency reached by some genomic variants. Using statistical analyses, demographic reconstructions, and molecular dynamics simulations, we show that the globally invasive G614 spike variant 1) underwent a significant demographic expansion in most countries explained neither by stochastic effects nor by overrepresentation in clinical samples, 2) increases the spike S1/S2 furin-like site conformational plasticity (short-range effect), and 3) modifies the internal motion of the receptor-binding domain affecting its cross-connection with other functional domains (long-range effect). Our results support the hypothesis of a selective advantage at the basis of the spread of the G614 variant, which we suggest may be due to structural modification of the spike protein at the S1/S2 proteolytic site, and provide structural information to guide the design of variant-specific drugs. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
07374038
Volume :
38
Issue :
5
Database :
Complementary Index
Journal :
Molecular Biology & Evolution
Publication Type :
Academic Journal
Accession number :
150175643
Full Text :
https://doi.org/10.1093/molbev/msaa337