SARS-CoV-2 susceptibility of domestic and wild mammals: is it all about the similarity of their ACE2 receptor to the human one?

Abstract

You have accessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Di Guardo Giovanni 2022SARS-CoV-2 susceptibility of domestic and wild mammals: is it all about the similarity of their ACE2 receptor to the human one?Proc. R. Soc. B.2892021256020212560http://doi.org/10.1098/rspb.2021.2560SectionYou have accessCommentSARS-CoV-2 susceptibility of domestic and wild mammals: is it all about the similarity of their ACE2 receptor to the human one? Giovanni Di Guardo† Giovanni Di Guardo http://orcid.org/0000-0003-4592-1084 Retired Professor of General Pathology and Veterinary Pathophysiology, Veterinary Medical Faculty, University of Teramo, Località Piano d'Accio, 64100 Teramo, Italy [email protected] Contribution: Writing – original draft Google Scholar Find this author on PubMed Search for more papers by this author Giovanni Di Guardo† Giovanni Di Guardo http://orcid.org/0000-0003-4592-1084 Retired Professor of General Pathology and Veterinary Pathophysiology, Veterinary Medical Faculty, University of Teramo, Località Piano d'Accio, 64100 Teramo, Italy [email protected] Contribution: Writing – original draft Google Scholar Find this author on PubMed Search for more papers by this author Published:02 February 2022https://doi.org/10.1098/rspb.2021.2560This article comments on the following:Research ArticlePredicting the zoonotic capacity of mammals to transmit SARS-CoV-2https://doi.org/10.1098/rspb.2021.1651 Ilya R. Fischhoff, Adrian A. Castellanos, João P. G. L. M. Rodrigues, Arvind Varsani and Barbara A. Han volume 288issue 1963Proceedings of the Royal Society B: Biological Sciences17 November 2021I read with great interest the article by Dr Ilya Fischhoff and co-workers, in which an elegant machine learning-based approach was successfully employed to predict the susceptibility of mammals to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), along with the zoonotic hazard posed by them. The three-dimensional model described by the aforementioned colleagues enabled prediction of the zoonotic potential of SARS-CoV-2 for more than 5000 domestic and wild mammals, with the obtained predictions being additionally corroborated by in vivo studies [1]. One of the main reasons underlying this work was represented by the comparatively much fewer mammalian species for which the primary amino acid sequences of their angiotensin-converting enzyme 2 (ACE2) viral host cell receptor are currently available.In this respect, however, adequate emphasis should be also placed upon the fact that a number of discrepancies have been reported between ACE2-expressing cells, on one side, and tissue tropism of SARS-CoV-2, on the other, with very low ACE2 expression levels having been found in respiratory and olfactory epithelial cells, despite their extremely frequent, if not constant, targeting by this viral pathogen [2].Noteworthy, two independent studies published in November 2020 in Science have shown that neuropilin-1 (NRP1), which is consistently expressed by respiratory, olfactory epithelial and endothelial cells, binds (similarly to ACE2) the furin-cleaved S1 fragment of SARS-CoV-2 spike glycoprotein, thereby potentiating infectivity and allowing viral entry into host cells [3,4]. This could also explain why a number of viruses such as human T-cell lymphotropic virus type 1 [5] and Epstein–Barr virus [6] use NRP1 for gaining entrance into susceptible host cells, given its high expression on epithelia facing the external environment and its role in enabling cell, vascular and tissue colonization.Within this framework, it would be interesting to comparatively investigate if and to what extent the different body cells and tissues from humans as well as from a number of SARS-CoV-2-susceptible mammals—either naturally/experimentally or suspectedly, based upon the herein commented machine learning approach [1]—express ACE2 and NRP1 simultaneously. Furthermore, the comparative study of the degree of primary amino acid sequence homology between human and animal ACE2 and NRP1 viral host cell receptors/coreceptors would probably clarify the SARS-CoV-2 susceptibility of the different species under investigation. This, in turn, could also allow a given animal species to act as a potentially valuable model in the comparative pathogenetic study of human SARS-CoV-2 infection, thus elucidating past and future ‘trajectories’ of this threatening viral agent, with special emphasis on its origin and on its ‘spillovers and spillbacks' from animals to mankind (and vice versa).Data accessibilityThis article has no additional data.Authors' contributionsG.D.G.: writing—original draft.Competing interestsI declare I have no competing interests.FundingI received no funding for this study.Footnotes†Present address: Viale Pasteur 77, 00144 EUR Rome, Italy.© 2022 The Author(s)Published by the Royal Society. All rights reserved.