ACE2 isoform diversity predicts the host susceptibility of SARS‐CoV‐2

Gao, Shan; Luan, Junwen; Cui, Haoran; Zhang, Leiliang

SARS‐CoV‐2 causes the ongoing COVID‐19 pandemic. ACE2 is the functional receptor for SARS‐CoV‐2. In our current study, we found that two types of deficient ACE2 isoforms from different mammals would compete with full length ACE2 for association with S protein. One type of ACE2 is a natural soluble isoform, the other type of ACE2 only associates with one loop of RBD of SARS‐CoV‐2 S protein. Mammals with either type of ACE2 will be deficient in support of SARS‐CoV‐2 entry. By combining S recognition and isoform analysis of ACE2, we predict that felids, mustelides, hamsters, and sheep are susceptible to SARS‐CoV‐2, while canids, swines, cattle and goats are not permissive for SARS‐CoV‐2. Thus, the differential susceptibilities of mammals with SARS‐CoV‐2 infection could be partially explained by the ACE2 isoform diversity. Our findings will shed important light on predicting the host range of other zoonotic viruses.