Identifying the Zoonotic Origin of SARS-CoV-2 by Modeling the Binding Affinity between the Spike Receptor-Binding Domain and Host ACE2

• DOI: 10.1021/acs.jproteome.0c00717
• Publication Date: 2020-11-11T19:56:12Z
• Authors: Xiaoqiang Huang; Chengxin Zhang; Robin Pearce; Gilbert S. Omenn; Yang Zhang
• Keywords: Coronavirus

Despite considerable research progress on SARS-CoV-2, the direct zoonotic origin (intermediate host) of virus remains ambiguous. The most definitive approach to identify intermediate host would be detection SARS-CoV-2-like coronaviruses in wild animals. However, due high number animal species, it is not feasible screen all species laboratory. Given that binding ACE2 proteins first step for invade cells, we propose a computational pipeline potential hosts SARS-CoV-2 by modeling affinity between Spike receptor-binding domain (RBD) and ACE2. Using this pipeline, systematically examined 285 variants from mammals, birds, fish, reptiles, amphibians, found energies calculated modeled Spike-RBD/ACE2 complex structures correlated closely with effectiveness infection as determined multiple experimental data sets. Built optimized cutoff, suggest set 96 including 48 experimentally investigated ones, which are permissive candidates primates, rodents, carnivores at highest risk infection. Overall, work only suggests limited range further investigation, but also, more importantly, proposes new structure-based general susceptibility analyses critical human infectious disease control wildlife protection.