Potential host range of multiple SARS-like coronaviruses and an improved ACE2-Fc variant that is potent against both SARS-CoV-2 and SARS-CoV-1

Yujun Li; Haimin Wang; Xiaojuan Tang; Danting Ma; Chengzhi Du; Yifei Wang; Hong Pan; Qing Zou; Jie Zheng; Liangde Xu; Michael Farzan; Guocai Zhong

Two subgroups of coronaviruses, including alphacoronaviruses (e.g. swine acute diarrhea syndrome 19 coronavirus, SADS-CoV) and betacoronaviruses (e.g. SARS coronavirus 1, SARS-CoV-1), infect 20 mammals and have broad host ranges spanning bats, rodents, domestic animals, and humans 1-7 . Bats 21 are considered to be the natural reservoir hosts for a number of pathogenic human coronaviruses, The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.10.032342 doi: bioRxiv preprint animals also served as intermediate hosts that facilitated SARS-CoV-2 transmission from its natural 30 reservoir hosts to humans. 31 As of April 7 th 2020, the uncontrolled COVID-19 pandemic has already caused over 1,210,000 32 confirmed infections and over 67,000 documented deaths across 211 countries, according to World 33 Health Organization's online updates. There are currently no vaccines or targeted therapeutics 34 available for this disease 11 . It is therefore urgent to study the host range of SARS-CoV-2 because Receptor binding is a critical determinant for the host range of coronaviruses 6,12 . SARS-CoV-2 utilizes 39 ACE2, the SARS-CoV-1 receptor 13 , as an essential cellular receptor to infect cells 8, 14, 15 . Therefore, in 40 this study, we characterized seventeen ACE2 orthologs for their function to support entry of SARS- 41 CoV-2, as well as that of SARS-CoV-1, a bat coronavirus (Bat-CoV RaTG13) ref. 8 , and a coronavirus 42 recently isolated from Malayan pangolins (called Pangolin-CoV hereafter) 16 . Furthermore, to explore 43 broadly anti-coronavirus approaches to treatment and prevention of SARS-CoV-2, we evaluated 44 recombinant receptor-binding domain (RBD) variants of the viral spike proteins, and soluble ACE2 45 variants for their potency as entry inhibitors against SARS-CoV-2 and SARS-CoV-1.