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.

在人类 SARS-CoV-2 的进化过程中，刺突糖蛋白 (S) 中出现了 D614G 替代物；含有这种替代物的病毒已成为 COVID-19 大流行中的主要流行变体¹. 然而，这种变体的日益流行是否反映了改善人类复制和/或传播的适应性优势，或者仅仅是由于创始人效应仍然未知。在这里，我们使用同基因 SARS-CoV-2 变体来证明含有 S(D614G) 的变体增强了与人细胞表面受体血管紧张素转换酶 2 (ACE2) 的结合，增加了在原代人支气管和鼻气道上皮细胞中的复制培养以及人类 ACE2 敲入小鼠模型中，并且在 SARS-CoV-2 感染的仓鼠和雪貂模型中显着增加了复制和传播性。我们的数据表明，S 中的 D614G 替代导致体外结合和复制的细微增加，并在体内提供了真正的竞争优势——尤其是在传输瓶颈期间。