SARS-CoV-2 spike D614G change enhances replication and transmission

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 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 ()
Additional contact information
Bin Zhou: CDC COVID-19 Response, Centers for Disease Control and Prevention
Tran Thi Nhu Thao: Institute of Virology and Immunology (IVI)
Donata Hoffmann: Friedrich-Loeffler-Institut
Adriano Taddeo: Institute of Virology and Immunology (IVI)
Nadine Ebert: Institute of Virology and Immunology (IVI)
Fabien Labroussaa: University of Bern
Anne Pohlmann: Friedrich-Loeffler-Institut
Jacqueline King: Friedrich-Loeffler-Institut
Silvio Steiner: Institute of Virology and Immunology (IVI)
Jenna N. Kelly: Institute of Virology and Immunology (IVI)
Jasmine Portmann: Institute of Virology and Immunology (IVI)
Nico Joel Halwe: Friedrich-Loeffler-Institut
Lorenz Ulrich: Friedrich-Loeffler-Institut
Bettina Salome Trüeb: University of Bern
Xiaoyu Fan: CDC COVID-19 Response, Centers for Disease Control and Prevention
Bernd Hoffmann: Friedrich-Loeffler-Institut
Li Wang: CDC COVID-19 Response, Centers for Disease Control and Prevention
Lisa Thomann: Institute of Virology and Immunology (IVI)
Xudong Lin: Battelle Memorial Institute
Hanspeter Stalder: Institute of Virology and Immunology (IVI)
Berta Pozzi: University of Bern
Simone Brot: University of Bern
Nannan Jiang: Oak Ridge Institute for Science and Education
Dan Cui: Battelle Memorial Institute
Jaber Hossain: CDC COVID-19 Response, Centers for Disease Control and Prevention
Malania M. Wilson: CDC COVID-19 Response, Centers for Disease Control and Prevention
Matthew W. Keller: CDC COVID-19 Response, Centers for Disease Control and Prevention
Thomas J. Stark: CDC COVID-19 Response, Centers for Disease Control and Prevention
John R. Barnes: CDC COVID-19 Response, Centers for Disease Control and Prevention
Ronald Dijkman: Institute of Virology and Immunology (IVI)
Joerg Jores: University of Bern
Charaf Benarafa: Institute of Virology and Immunology (IVI)
David E. Wentworth: CDC COVID-19 Response, Centers for Disease Control and Prevention
Volker Thiel: Institute of Virology and Immunology (IVI)
Martin Beer: Friedrich-Loeffler-Institut

Nature, 2021, vol. 592, issue 7852, 122-127

Abstract: Abstract During 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.

Date: 2021
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DOI: 10.1038/s41586-021-03361-1

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