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SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals

Lam, SD; Bordin, N; Waman, VP; Scholes, HM; Ashford, P; Sen, N; van Dorp, L; ... Orengo, CA; + view all (2020) SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals. BioRxiv: Cold Spring Harbor, NY, USA. Green open access

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Abstract

SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.

Type: Working / discussion paper
Title: SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals
Open access status: An open access version is available from UCL Discovery
DOI: 10.1101/2020.05.01.072371
Publisher version: http://dx.doi.org/10.1101/2020.05.01.072371
Language: English
Additional information: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license (http://creativecommons.org/licenses/by-nd/4.0/).
Keywords: SARS-CoV-2, COVID-19, spike protein, ACE2, TMPRSS2, structural bioinformatics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > STEaPP
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10189532
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