SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility
Tran Thi Nhu Thao,
Nico Joel Halwe,
Bettina Salome Trueb,
Jenna Nicole Kelly,
Simone de Brot,
Matthew W. Keller,
Thomas J Stark,
John R. Barnes,
David E Wentworth,
Posted 27 Oct 2020
bioRxiv DOI: 10.1101/2020.10.27.357558
Posted 27 Oct 2020
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 pandemic. 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 Statement The authors have declared no competing interest.
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