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

ZHOU, BIN; THAO, TRAN THI NHU; 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; POZZI, BERTA; DE BROT, SIMONE; JIANG, NANNAN; CUI, DAN; HOSSAIN, JABER; WILSON, MALANIA M.; KELLER, MATTHEW W.; STARK, THOMAS J.; BARNES, JOHN R.; DIJKMAN, RONALD; JORES, JOERG; BENARAFA, CHARAF; WENTWORTH, DAVID E.; THIEL, VOLKER; BEER, MARTIN

NATURE

NATURE PUBLISHING GROUP

Año: 2021 vol. 592 p. 122 - 127

0028-0836

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.