The coronavirus disease 2019 (COVID-19) pandemic underscores the need to better understand animal-to-human transmission of coronaviruses and adaptive evolution within new hosts. We scanned more than 182,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes for selective sweep signatures and found a distinct footprint of positive selection located around a non-synonymous change (A1114G; T372A) within the spike protein receptor-binding domain (RBD), predicted to remove glycosylation and increase binding to human ACE2 (hACE2), the cellular receptor. This change is present in all human SARS-CoV-2 sequences but not in closely related viruses from bats and pangolins. As predicted, T372A RBD bound hACE2 with higher affinity in experimental binding assays. We engineered the reversion mutant (A372T) and found that A372 (wild-type [WT]-SARS-CoV-2) enhanced replication in human lung cells relative to its putative ancestral variant (T372), an effect that was 20 times greater than the well-known D614G mutation. Our findings suggest that this mutation likely contributed to SARS-CoV-2 emergence from animal reservoirs or enabled sustained human-to-human transmission.

2019 年冠状病毒病 (COVID-19) 大流行强调需要更好地了解冠状病毒从动物到人类的传播以及新宿主内的适应性进化。我们扫描了超过 182,000 个严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 基因组以获取选择性扫描特征，并在刺突蛋白受体结合内的非同义变化（A1114G；T372A）周围发现了明显的阳性选择足迹结构域 (RBD)，预计会去除糖基化并增加与细胞受体人类 ACE2 (hACE2) 的结合。这种变化存在于所有人类 SARS-CoV-2 序列中，但不存在于来自蝙蝠和穿山甲的密切相关的病毒中。正如预测的那样，T372A RBD 在实验结合测定中以更高的亲和力结合 hACE2。我们设计了逆转突变体 (A372T)，发现 A372（野生型 [WT]-SARS-CoV-2）相对于其假定的祖先变异体 (T372) 增强了人肺细胞的复制，其效果是 A372 的 20 倍众所周知的 D614G 突变。我们的研究结果表明，这种突变可能促成了 SARS-CoV-2 从动物宿主中出现或实现了持续的人际传播。