SARS-CoV-2 is closely related to SARS-CoV, which caused a more limited outbreak in several countries in 2003 ( Peiris et al., 2003 Rota et al., 2003) however, several bat- and pangolin-derived viruses are even more closely related to SARS-CoV-2, indicative of a zoonotic origin ( Lam et al., 2020 Xiao et al., 2020 Zhou et al., 2020a). The virus was first described in late 2019 in Wuhan, China, and quickly spread globally ( Zhou et al., 2020b). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused over 155 million infections with at least 3.2 million deaths worldwide as of early May 2021. Our findings suggest that this mutation likely contributed to SARS-CoV-2 emergence from animal reservoirs or enabled sustained human-to-human transmission. We engineered the reversion mutant (A372T) and found that A372 (wild-type -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. As predicted, T372A RBD bound hACE2 with higher affinity in experimental binding assays. This change is present in all human SARS-CoV-2 sequences but not in closely related viruses from bats and pangolins. 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. 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.
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