RT Journal Article
SR Electronic
T1 SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.27.357558
DO 10.1101/2020.10.27.357558
A1 Bin Zhou
A1 Tran Thi Nhu Thao
A1 Donata Hoffmann
A1 Adriano Taddeo
A1 Nadine Ebert
A1 Fabien Labroussaa
A1 Anne Pohlmann
A1 Jacqueline King
A1 Jasmine Portmann
A1 Nico Joel Halwe
A1 Lorenz Ulrich
A1 Bettina Salome Trüeb
A1 Jenna N. Kelly
A1 Xiaoyu Fan
A1 Bernd Hoffmann
A1 Silvio Steiner
A1 Li Wang
A1 Lisa Thomann
A1 Xudong Lin
A1 Hanspeter Stalder
A1 Berta Pozzi
A1 Simone de Brot
A1 Nannan Jiang
A1 Dan Cui
A1 Jaber Hossain
A1 Malania Wilson
A1 Matthew Keller
A1 Thomas J. Stark
A1 John R. Barnes
A1 Ronald Dijkman
A1 Joerg Jores
A1 Charaf Benarafa
A1 David E. Wentworth
A1 Volker Thiel
A1 Martin Beer
YR 2020
UL http://biorxiv.org/content/early/2020/10/27/2020.10.27.357558.abstract
AB 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 pandemic1. 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.Competing Interest StatementThe authors have declared no competing interest.