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

Abstract

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.

Spillback in the Anthropocene: the risk of human-to-wildlife pathogen transmission for conservation and public health

“…Although model results are not always well-integrated into pandemic prevention efforts (Holmes et al 2018;Carlson 2020), they are crucial for understanding broad-scale patterns of zoonotic spilloverand the same will be true of spillback. As it stands, researchers have just produced a model-based prediction of spillback risk for the most intensively-studied pathogen in recent years (SARS-CoV-2 (Fischhoff et al 2021)), and given enough data on broad-scale spillback trends, we may be able to do the same more broadly in the near future.…”

“…For example, models are often framed as "predicting the original reservoir host(s)" (Babayan et al 2018;Becker et al 2020;Brierley & Fowler 2020), rather than "predicting potential future reservoir hosts." This is also often true of laboratory infection studies (Botten et al 2000;Richter et al 2004;Cogswell-Hawkinson et al 2012;Jones et al 2019), although work on SARS-CoV-2 is a notable exception given the concern over spillback (Fagre et al 2020;Griffin et al 2020;Hall et al 2020;Schlottau et al 2020;Fischhoff et al 2021). Because of the different ways that we obtain and interpret human and animal infection data, it remains a near-total unknown whether these approaches are equally valid, whether spillover and spillback are symmetrical processes, and whether the answers to these questions depend heavily on the host and pathogen of interest (Box 1); nevertheless, this symmetry is sometimes implicitly assumed to be the case.…”

“…First, while spillover and spillback plausibly follow a similar set of rules, these rules do not necessarily act symmetrically on transmission to and from humans (see Box 1). Researchers may be able to construct models of spillback risk based on spillover-related processes and then to test their predictions with spillback datasets, or vice versa, in order to verify whether these approaches are valid (Fischhoff et al 2021). Second, while it is likely universally useful to understand and predict how pathogens transmit from animals to humans, it is possible that a smaller subset of spillback-related frontiers will be worthy of (urgent) consideration or investment in mitigation.…”

Zoonotic Risk Technology Enters the Viral Emergence Toolkit

“…Decomposing viral genomes, and identifying the regions most relevant to zoonotic emergence, can open new avenues for advanced modeling that goes beyond pattern recognition. For example, researchers have developed a number of structural simulations to explore binding affinity between the spike protein of SARS-CoV-2 and ACE2 receptors in animal and human cells [61,62], and structural modeling can be paired with other trait data to better predict the capacity for various mammal species to transmit SARS-CoV-2 [63].…”

COVID-19 and Preparing for Future Ecological Crises: Hopes from Metagenomics in Facing Current and Future Viral Pandemic Challenges

“…The plasticity of RNA viruses also increases the likelihood of a ''reverse'' spillover from humans to a new wild or domesticated animal reservoir. In silico studies have highlighted that the spike protein of SARS-CoV-2 can proficiently bind the angiotensin-converting enzyme (ACE) receptor of a wide range of mammals (Fischhoff et al, 2021;Luan et al, 2020;Zhai et al, 2020). Experimental study has then confirmed that SARS-CoV-2 can infect several mammals, including hamsters (Chan et al, 2020;Sia et al, 2020;Trimpert et al, 2020), monkeys (Woolsey et al, 2021), ferrets (Richard et al, 2020;Schlottau et al, 2020), and minks (Koopmans, 2021;Munnink et al, 2021).…”