In Silico Analysis of Intermediate Hosts and Susceptible Animals of SARS-CoV-2

COVID-19, caused by SARS-CoV-2 with major symptom of pneumonia is bringing huge disasters to the people around the world. Recent research indicates that the natural host of SARS-CoV-2 may be bats, but its intermediate host is still unclear. Only by finding natural and intermediate host for SARS-CoV-2 can cut off the source and prevent the virus from being transmitted to humans. In this study, we established a new method for the mining of intermediate host. We selected 82 representative ACE2 sequences from the 1000 sequences with the closest homology to the human ACE2 protein. All these selected ACE2 proteins were modeled by homology modeling. The potential natural and intermediate hosts, as well as susceptible animals of SARS-CoV-2 were analyzed systematically by calculating the binding free energy of ACE2 protein with the RBD of SARS-CoV-2. Based on this study, Rhinolophus sinicus was suggested to be the natural host, and the virus may be transmitted directly from bats to humans. Primates, some wild Felidae, civet, goats, spotted hyenas and golden hamsters may be susceptible to SARS-CoV-2 and could be intermediate hosts, while pangolins are unlikely to be intermediate hosts, and birds and reptiles are not intermediate hosts. Mice, rats and guinea pig are not susceptible to SARS-CoV-2. Considering the possible susceptibility of non-human primates, goats and golden hamsters, they can be used as experimental animals directly for the SARS-CoV-2 infection models without transgenic operation. Herein, the possible candidates of natural and intermediate hosts of SARS-CoV-2 were suggested, which will provide guiding significance for subsequent researches.