SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility | bioRxiv preprints (not peer reviewed)

Type Journal Article Author Bin Zhou Author Tran Thi Nhu Thao Author Donata Hoffmann Author Adriano Taddeo Author Nadine Ebert Author Fabien Labroussaa Author Anne Pohlmann Author Jacqueline King Author Jasmine Portmann Author Nico Joel Halwe Author Lorenz Ulrich Author Bettina Salome Trüeb Author Jenna N. Kelly Author Xiaoyu Fan Author Bernd Hoffmann Author Silvio Steiner Author Li Wang Author Lisa Thomann Author Xudong Lin Author Hanspeter Stalder Author Berta Pozzi Author Simone de Brot Author Nannan Jiang Author Dan Cui Author Jaber Hossain Author Malania Wilson Author Matthew Keller Author Thomas J. Stark Author John R. Barnes Author Ronald Dijkman Author Joerg Jores Author Charaf Benarafa Author David E. Wentworth Author Volker Thiel Author Martin Beer URL https://www.biorxiv.org/content/10.1101/2020.10.27.357558v1 Rights © 2020, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-NoDerivs 4.0 International), CC BY-ND 4.0, as described at http://creativecommons.org/licenses/by-nd/4.0/ Pages 2020.10.27.357558 Publication bioRxiv Date 27/10/2020 Extra Publisher: Cold Spring Harbor Laboratory Section: New Results DOI 10.1101/2020.10.27.357558 Library Catalog www.biorxiv.org Language en 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 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.