• Bin Zhou, Tran Thi Nhu Thao, Donata Hoffmann, Adriano Taddeo, Nadine Ebert, Fabien Labroussaa, Anne Pohlmann, Jacqueline King, Silvio Steiner, Jenna N Kelly, Jasmine Portmann, Nico Joel Halwe, Lorenz Ulrich, Bettina Salome Trüeb, Xiaoyu Fan, Bernd Hoffmann, Li Wang, Lisa Thomann, Xudong Lin, Hanspeter Stalder, Berta Pozzi, Simone de Brot, Nannan Jiang, Dan Cui, Jaber Hossain, Malania M Wilson, Matthew W Keller, Thomas J Stark, John R Barnes, Ronald Dijkman, Joerg Jores, Charaf Benarafa, David E Wentworth, Volker Thiel, and Martin Beer.
• CDC COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, GA, USA.
• Nature. 2021 Apr 1; 592 (7852): 122-127.

AbstractDuring the evolution of SARS-CoV-2 in humans, a D614G substitution in the spike glycoprotein (S) has emerged; virus containing this substitution has become the predominant circulating variant in the COVID-19 pandemic1. However, whether the increasing prevalence of this variant reflects a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains unknown. Here we use isogenic SARS-CoV-2 variants to demonstrate that the variant that contains S(D614G) has enhanced binding to the human cell-surface receptor angiotensin-converting enzyme 2 (ACE2), increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a human ACE2 knock-in mouse model, and markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Our data show that the D614G substitution in S results in subtle increases in binding and replication in vitro, and provides a real competitive advantage in vivo-particularly during the transmission bottleneck. Our data therefore provide an explanation for the global predominance of the variant that contains S(D614G) among the SARS-CoV-2 viruses that are currently circulating.

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