Comparative ACE2 variation and primate COVID-19 risk

Amanda D. Melin; Mareike C. Janiak; Frank Marrone; Paramjit S. Arora; James P. Higham

Consistent with our results, infection studies show that rhesus monkeys can be successfully infected with SARS-CoV-2, and go on to develop COVID-19 like symptoms 8, 9 . Our results based on protein modeling offer better news for monkeys in the Americas (platyrrhines). There are three differences in amino acid residues between platyrrhines and catarrhines, and two of these, H41Y and E42Q show strong evidence of being impactful changes. These amino acid changes are modeled to reduce the binding affinity between SARS-CoV-2 and ACE2 by ca. 400-fold. Similar reduced susceptibility is predicted for tarsiers, and two of the three lemurs and lorisoids (strepsirrhines). One of the analyzed lemurs, Coquerel's sifaka, has fewer differences from catarrhines at important binding sites, including possessing the high-risk residue variant at site 41, and as such is also predicted to be highly susceptible. Nonetheless, these are only predicted results based on amino acid residues, and protein-protein interaction models. We urge extreme caution in using our analyses as the basis for relaxing policies regarding the protection of platyrrhines and strepsirrhines. Experimental assessment of synthetic protein interactions can . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.09.034967 doi: bioRxiv preprint now occur in the laboratory e.g. 36 , and confirmation of our model predictions should be sought before any firm conclusions are reached.