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SARS-CoV-2 spike D614G change enhances replication and transmission #MMPMID33636719
Zhou B; Thao TTN; Hoffmann D; Taddeo A; Ebert N; Labroussaa F; Pohlmann A; King J; Steiner S; Kelly JN; Portmann J; Halwe NJ; Ulrich L; Trueb BS; Fan X; Hoffmann B; Wang L; Thomann L; Lin X; Stalder H; Pozzi B; de Brot S; Jiang N; Cui D; Hossain J; Wilson MM; Keller MW; Stark TJ; Barnes JR; Dijkman R; Jores J; Benarafa C; Wentworth DE; Thiel V; Beer M
Nature 2021[Apr]; 592 (7852): 122-127 PMID33636719show ga
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 pandemic(1). 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.
Nature 2021 ; 592 (7852): 122-127
