Broad and differential animal ACE2 receptor usage by SARS-CoV-2

Xuesen Zhao; Danying Chen; Robert Szabla; Mei Zheng; Guoli Li; Pengcheng Du; Shuangli Zheng; Xinglin Li; Chuan Song; Rui Li; Ju-Tao Guo; Murray Junop; Hui Zeng; Hanxin Lin

his preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.19.048710 doi: bioRxiv preprint 11 disrupted in only bat ACE2s occurs at position H34. In humans, H34 forms a H-bond 231 with Y453 from the RBD, which is broken through a H34T substitution in bat ACE2s. 232 Finally, the bat-unique substitution E329N appears to be disrupting H-bonds connecting 233 two ACE2 residues (E329, Q325) and two RBD residues (N439, Q506). In Tb bat ACE2, 234 all connections in the H-bond network are disrupted by the single E329N substitution, 235 however the H-bond network is predicted to be restored by an additional substitution, 236 Q325E in Rs bat. In addition, other residue substitutions, i.e. T27M and M82N in Rs bat, 237 and D30Q and L79H in Tb bat, are also disruptive (Fig. 6) . 238 These results reveal that the poor and low receptor activity of rodent ACEs and bat 239 ACE2 are resulted from a broken interaction network by a key residue substitution, i.e. 240 K353H in rodents and Y41H in bats, and additive disruptive effects by multiple residue 241 substitutions.