SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility

BioRxiv : the Preprint Server for Biology
Bin ZhouMartin Beer

Abstract

During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic 1 . However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human ACE2, (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro , it provides a real competitive advantage in vivo , particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.

Citations

Jan 30, 2021·World Journal of Clinical Cases·Si ChenLi-Ying Zhang
Feb 16, 2021·Science China. Life Sciences·Aria C Shi, Xuping Xie

Methods Mentioned

BETA
biolayer interferometry
flow cytometry
Bio-layer
biosensors
PCR
amplicon sequencing
amplicon

Related Concepts

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