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

  1. SD Lam
  2. N Bordin
  3. VP Waman
  4. HM Scholes
  5. P Ashford
  6. N Sen
  7. L van Dorp
  8. C Rauer
  9. NL Dawson
  10. CSM Pang
  11. M Abbasian
  12. I Sillitoe
  13. SJL Edwards
  14. F Fraternali
  15. JG Lees
  16. JM Santini
  17. CA Orengo

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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.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.01.072371: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    TMPRSS2 protein sequences for 278 vertebrate sequences, including the human sequence, were obtained from ENSEMBL (Supplementary Table 2).
    ENSEMBL
    suggested: (Ensembl, RRID:SCR_002344)
    We generated query–template alignments using HH-suite[73] and predicted 3D models using MODELLER v.
    MODELLER
    suggested: (MODELLER, RRID:SCR_008395)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Although we felt that these faster methods were justified by the need for timely answers to these questions, there are clearly caveats to our work that should be taken into account. Whilst we use a state of the art modelling tool[64] and an endorsed method for calculating changes in energy of the complex[65], molecular dynamics may give a more accurate picture of energy changes by sampling rotamer space more comprehensively[29]. However, such an approach would have been prohibitively expensive at a time when it is clearly important to identify animals at risk as quickly as possible. Each animal could take orders of magnitude longer to analyse using molecular dynamics. Further caveats include the fact that although the animals we highlight at risk from our changes in binding energy calculations correlate well with the experimental data, there is only a small amount of such data currently available, and many of the experimental papers reporting these data are yet to be peer reviewed. Finally, we restricted our analyses to one strain of SARS-CoV-2, but other strains may have evolved with mutations that give more complementary interfaces. For example, recent work suggests SARS-CoV-2 can readily adapt to infect mice following serial passages[66]. In summary, our work is not aiming to provide an absolute measure of risk of infection. Rather, it should be considered an efficient method to screen a large number of animals and suggest possible susceptibility, and thereby guide further...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.05.01.072371 on bioRxiv