%0 Journal Article %A Bin Zhou %A Tran Thi Nhu Thao %A Donata Hoffmann %A Adriano Taddeo %A Nadine Ebert %A Fabien Labroussaa %A Anne Pohlmann %A Jacqueline King %A Jasmine Portmann %A Nico Joel Halwe %A Lorenz Ulrich %A Bettina Salome Trüeb %A Jenna N. Kelly %A Xiaoyu Fan %A Bernd Hoffmann %A Silvio Steiner %A Li Wang %A Lisa Thomann %A Xudong Lin %A Hanspeter Stalder %A Berta Pozzi %A Simone de Brot %A Nannan Jiang %A Dan Cui %A Jaber Hossain %A Malania Wilson %A Matthew Keller %A Thomas J. Stark %A John R. Barnes %A Ronald Dijkman %A Joerg Jores %A Charaf Benarafa %A David E. Wentworth %A Volker Thiel %A Martin Beer %T SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility %D 2020 %R 10.1101/2020.10.27.357558 %J bioRxiv %P 2020.10.27.357558 %X 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. %U https://www.biorxiv.org/content/biorxiv/early/2020/10/27/2020.10.27.357558.full.pdf