In contrast, certain significant changes occur in the mouse and/or rat ACE2 compared to the human one (Fig. 1). The Asn31 and Ser82 in mouse ACE2 may not form favorable interactions with 2019-nCoV due to their electrostatic or hydrophilic characteristics. Importantly, the change into His353 in both mouse and rat ACE2 does not form a strong salt bridge as Lys353 does. Since the structural information for mouse and rat ACE2 is unavailable, we carried out homology modeling using human ACE2 (PDB code 2AJF) as template on online (https://swissmodel.expasy.org) for further analyses. In Fig. 2 A, the change into Ser82 in mouse ACE2 may interfere with the hydrophobic interaction of the original Met82. Additionally, the changes into Asn31 and His353 definitely affect the salt bridge formation and electrostatic potential. The change into His353 in rat ACE2 is similar in the effect on receptor-virus interaction (Fig. 2B). These analyses partially explain why mouse ACE2 does not mediate 2019-nCoV infection reported by Zheng-Li Shi et al. and assume that rodents are not likely to be the susceptible host.
Fig. 2 Structural analyses of the human ACE2 (PDB code 2AJF) with the modeled mouse (A) and rat (B) ones in cartoon diagrams and surface electrostatic potential maps. The regions 30–41, 82–84 and 353–357 are enlarged and the critical residues are labeled. The changed ones affecting the electrostatic potential are labeled and circled in dashed lines. The electrostatic potential is colored from −62 to +62 kiloteslas/charge.