Predicting the zoonotic capacity of mammals to transmit SARS-CoV-2.

Back and forth transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between humans and animals will establish wild reservoirs of virus that endanger long-term efforts to control COVID-19 in people and to protect vulnerable animal populations. Better targeting surveillance and laboratory experiments to validate zoonotic potential requires predicting high-risk host species. A major bottleneck to this effort is the few species with available sequences for angiotensin-converting enzyme 2 receptor, a key receptor required for viral cell entry. We overcome this bottleneck by combining species' ecological and biological traits with three-dimensional modelling of host-virus protein-protein interactions using machine learning. This approach enables predictions about the zoonotic capacity of SARS-CoV-2 for greater than 5000 mammals-an order of magnitude more species than previously possible. Our predictions are strongly corroborated by <i>in vivo</i> studies. The predicted zoonotic capacity and proximity to humans suggest enhanced transmission risk from several common mammals, and priority areas of geographic overlap between these species and global COVID-19 hotspots. With molecular data available for only a small fraction of potential animal hosts, linking data across biological scales offers a conceptual advance that may expand our predictive modelling capacity for zoonotic viruses with similarly unknown host ranges.