Bin Zhou, T. T. N. Thao, D. Hoffmann, A. Taddeo, Nadine Ebert, Fabien Labroussaa, A. Pohlmann, Jacqueline King, J. Portmann, N. Halwe, Lorenz Ulrich, B. Trüeb, Jenna N. Kelly, Xiaoyu Fan, B. Hoffmann, Silvio Steiner, L. Wang, Lisa Thomann, Xudong Lin, H. Stalder, B. Pozzi, S. de Brot, Nannan Jiang, Dan Cui, Jaber Hossain, M. Wilson, Matthew W Keller, T. Stark, J. Barnes, R. Dijkman, J. Jores, C. Benarafa, D. Wentworth, V. Thiel, M. Beer
bioRxiv : the preprint server for biology, 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 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.
Cited by 30 publications.
Field of study: Biology