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

be able to efficiently infect wildtype mice. 356 To date, several animals (i.e. rhesus monkey, ferret, dog, cat, pig, chicken and duck) 357 have been examined as potential animal models for SARS-CoV-2 37,38 . Although the 358 rhesus monkey, ferret and cat may seem to be the promising candidates, none of them 359 are perfect in terms of recapitulation of typical clinical features in COVID-19 patients. 360 Therefore, multiple animal models may be needed. Our results indicate that rabbit 361 ACE2 is a more efficient receptors than other animal ACE2s for both SARS-CoV-2 and 362 SARS-CoV (Fig.3) . Therefore, it may be worthy assessing rabbit as a useful animal 363 model for further studies. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.19.048710 doi: bioRxiv preprint 1h at room temperature. After three-time washes, the proteins bounded with antibodies 414 were imaged with the Li-Cor Odyssey system. (Li-Cor Biotechnology). 415 Immunoprecipitation (IP) assay. 416 The association between Ig-fused S1 protein or RBD protein and ACE2 protein 417 with C9 tag was measured by IP according to a previously described method 30 CoVs. The S1 subunit is required for binding to ACE2 receptor, while the S2 subunit 491 containing a FP mediates membrane fusion. In SARS-CoV-2, the S1 contains NTD and The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.19.048710 doi: bioRxiv preprint ACE2 Q24 H-bond -------------24 Q RBD N487 H-bond -T T D T D D D D D D D T ACE2 S12 H-bond -D D T T D D D D D D D D 27 T RBD Y489 VdW -D T D ---------RBD A475 VdW -D T D ---------RBD F456 VdW -D T D ---------28 F ACE2 Y83 π -------------30 D RBD K417 H-bond --D D D T T T T T T T T 31 K RBD Q493 H-bond --T -D D ---- Q42 H-bond -----T T T T T T -T ACE2 K353 H-bond -----T T T T T T -T RBD Q498 H-bond -----T T T T T T -T RBD Y449