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

S D Lam,M Abbasian,N Bordin,N L Dawson,V P Waman,J G Lees,S J L Edwards,P Ashford,L Van Dorp,C Rauer,I Sillitoe,H M Scholes,C A Orengo,J M Santini,C S M Pang,N Sen,F Fraternali

doi:10.1038/s41598-020-71936-5

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.

Highlights

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
Our results suggest that SARS-CoV-2 could infect a broad range of vertebrates, which could serve as reservoirs of the virus, supporting future anthroponotic and zoonotic transmission
Most orthologues have more than 60% sequence identity with human angiotensin I converting enzyme 2 (ACE2) (Supplementary Fig. 1A)

Summary

Introduction

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. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. Little work has been done to assess the animal reservoirs of SARS-CoV-2, or the potential for the virus to spread to other species living with, or in close proximity to, humans in domestic, rural, agricultural or zoological settings. Coronaviruses, including SARS-CoV-2, are major multi-host pathogens and can infect a wide range of nonhuman animals[3,4,5]. Severe acute respiratory syndrome coronavirus (SARS-CoV), the betacoronavirus that caused the 2002–2004 SARS outbreak[12], likely jumped to humans from its original bat host via civets

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Conclusion