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

submitted on 01.04.2020, 14:59 and posted on 03.04.2020, 10:29 by Canrong Wu, Mengzhu Zheng, Yueying Yang, Mingxue Li, Yang Liu, Peng Zhang, Yali Wang, Qiqi Wang, Yang Xu, Lixia Chen, Hua Li
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.


the Fundamental Research Fund for the Central Universities (HUST COVID-19 Rapid Response Call, No. 2020kfyXGYJ037).

National Mega-project for Innovative Drugs (grant number 2019ZX09721001-004-007)

National Natural Science Foundation of China (NSFC) (grant number No.U1803122, 81773637, 81773594, U1703111)


Email Address of Submitting Author


Huazhong University of Science & Technology



ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest.