PT - JOURNAL ARTICLE AU - Ilya R. Fischhoff AU - Adrian A. Castellanos AU - João P.G.L.M. Rodrigues AU - Arvind Varsani AU - Barbara A. Han TI - Predicting the zoonotic capacity of mammal species for SARS-CoV-2 AID - 10.1101/2021.02.18.431844 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.02.18.431844 4099 - http://biorxiv.org/content/early/2021/02/19/2021.02.18.431844.short 4100 - http://biorxiv.org/content/early/2021/02/19/2021.02.18.431844.full AB - Spillback transmission from humans to animals, and secondary spillover from animal hosts back into humans, have now been documented for SARS-CoV-2. In addition to threatening animal health, virus variants arising from novel animal hosts have the potential to undermine global COVID-19 mitigation efforts. Numerous studies have therefore investigated the zoonotic capacity of various animal species for SARS-CoV-2, including predicting both species’ susceptibility to infection and their capacities for onward transmission. A major bottleneck to these studies is the limited number of sequences for ACE2, a key cellular receptor in chordates that is required for viral cell entry. Here, we combined protein structure modeling with machine learning of species’ traits to predict zoonotic capacity of SARS-CoV-2 across 5,400 mammals. High accuracy model predictions were strongly corroborated by in vivo empirical studies, and identify numerous mammal species across global COVID-19 hotspots that should be prioritized for surveillance and experimental validation.Competing Interest StatementThe authors have declared no competing interest.