Zhou, Bin; Tran, Thi Nhu Thao; Hoffmann, Donata; Taddeo, Adriano; Ebert, Nadine; Labroussaa, Fabien; Pohlmann, Anne; King, Jacqueline; Steiner, Silvio; Kelly, Jenna N.; Portmann, Jasmine; Halwe, Nico Joel; Ulrich, Lorenz; Trüeb, Bettina Salome; Fan, Xiaoyu; Hoffmann, Bernd; Wang, Li; Thomann, Lisa; Lin, Xudong; Stalder, Hanspeter; ... (2021). SARS-CoV-2 spike D614G change enhances replication and transmission. Nature, 592(7852), pp. 122-127. Springer Nature 10.1038/s41586-021-03361-1
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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.
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