Comparative tropism profiling of SARS-CoV-2, SARS-CoV, and MERS-CoV in mammals

Zoonotic coronavirus epidemics, like COVID-19, SARS, and MERS, have caused giant losses to public health. Exploring wild reservoirs of SARS-CoV-2 is critical to long-term control and prediction of the future scenarios of COVID-19, which is limited by inadequate information about the susceptible host range. Here, we performed a comparative in vitro infection analysis of 83 cell cultures derived from 55 mammals using pseudotyped viruses bearing S proteins from SARS-CoV-2, SARS-CoV, and MERS-CoV. We found cell cultures from Thomas's horseshoe bat and king horseshoe bat are highly susceptible to SARS-CoV-2, SARS-CoV, and MERS-CoV pseudotyped viruses. Moreover, five mutations (del69-70, D80Y, S98F, T572I, and Q675H) were found to significantly affect the host tropism of SARS-CoV-2. Examination of the phylogenetic signals of transduction rates reveals that closely-related taxa generally have similar susceptibility to MERS-CoV, but not SARS-CoV and SARS-CoV-2 pseudotyped viruses. By profiling the gene expression of cell lines, we finally identified several genes including PDZK1, SERPINF2, and RBMX whose expressions are strongly correlated with infection ability across phylogeny. Our study provides a basic document of potential risk, mutations, and host factors that underlined cross-species transmission of SARS-CoV-2.