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 i) underwent a significant demographic expansion in most countries not explained by stochastic effects nor by overrepresentation in clinical samples; ii) increases the spike S1/S2 furin-like site conformational plasticity (short-range effect), and iii) 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 provides structural information to guide the design of variant-specific drugs.

Population dynamics and structural effects at short and long range support the hypothesis of the selective advantage of the G614 SARS-Cov2 spike variant / Trucchi, Emiliano; Gratton, Paolo; Mafessoni, Fabrizio; Motta, Stefano; Cicconardi, Francesco; Mancia, Filippo; Bertorelle, Giorgio; D'Annessa, Ilda; Marino, Daniele Di. - In: MOLECULAR BIOLOGY AND EVOLUTION. - ISSN 0737-4038. - 38:5(2021), pp. 1966-1979. [10.1093/molbev/msaa337]

Population dynamics and structural effects at short and long range support the hypothesis of the selective advantage of the G614 SARS-Cov2 spike variant

Trucchi, Emiliano
;
Marino, Daniele Di
Ultimo
2021-01-01

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 i) underwent a significant demographic expansion in most countries not explained by stochastic effects nor by overrepresentation in clinical samples; ii) increases the spike S1/S2 furin-like site conformational plasticity (short-range effect), and iii) 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 provides structural information to guide the design of variant-specific drugs.
2021
File in questo prodotto:
File Dimensione Formato  
msaa337.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza d'uso: Creative commons
Dimensione 1.82 MB
Formato Adobe PDF
1.82 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/286598
Citazioni
  • ???jsp.display-item.citation.pmc??? 14
  • Scopus 19
  • ???jsp.display-item.citation.isi??? 20
social impact