Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. This study examined several VOCs (Alpha, Beta, Gamma, Mink-Y453F, Mink-F486L, and Mink-N501T) and found that five variants' receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants' pseudoviruses increased entry into susceptible cells. Crystal structures of hACE2-RBD complexes identified key residues facilitating changes in hACE2 binding affinity. Soluble hACE2 protein efficiently prevented most variants' pseudoviruses. These findings provide important molecular information for developing novel therapeutic and prophylactic agents.
