4.7 Article

Predicted structural mimicry of spike receptor-binding motifs from highly pathogenic human coronaviruses

Journal

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
Volume 19, Issue -, Pages 3938-3953

Publisher

ELSEVIER
DOI: 10.1016/j.csbj.2021.06.041

Keywords

SARS-CoV-2; SARS-CoV; MERS-CoV; Coronavirus spike protein; COVID-19; Viral host mimicry; Infectious disease; Structural bioinformatics

Funding

  1. American Leprosy Missions, United States of America [G88726]
  2. Wellcome Trust [107032AIA, 200814/Z/16/Z]
  3. Antibiotic Research UK [PHZJ/687]
  4. Biotechnology and Biological Sciences Research Council (BBSRC) DTP studentship [BB/M011194/1]
  5. King Abdullah scholarship (Saudi Arabia Research Council)
  6. Ipsen Bioinnovation [PHZJ/487 -RG83343]
  7. Biotechnology and Biological Sciences Research Council (BBSRC) [BB/N00468X/1]
  8. UK Cystic Fibrosis Trust (Innovation Hub grant) [001]
  9. NIHR Cambridge Biomedical Research Centre
  10. Cystic Fibrosis Trust [RG 70975]
  11. Fondation Botnar [RG91317]
  12. Brazilian National Council for Scientific and Technological Development (CNPq)
  13. BBSRC [BB/N00468X/1] Funding Source: UKRI

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The study explores the potential mimicry of receptor-binding motifs on the spike proteins of three coronaviruses, revealing similarities to both human and non-human proteins. This indicates pathways utilized by the spike proteins and possible shared host interactions, guiding experimental efforts to understand interactions between human and coronavirus proteins.
Viruses often encode proteins that mimic host proteins in order to facilitate infection. Little work has been done to understand the potential mimicry of the SARS-CoV-2, SARS-CoV, and MERS-CoV spike proteins, particularly the receptor-binding motifs, which could be important in determining tropism and druggability of the virus. Peptide and epitope motifs have been detected on coronavirus spike proteins using sequence homology approaches; however, comparing the three-dimensional shape of the protein has been shown as more informative in predicting mimicry than sequence-based comparisons. Here, we use structural bioinformatics software to characterize potential mimicry of the three coronavirus spike protein receptor-binding motifs. We utilize sequence-independent alignment tools to compare structurally known protein models with the receptor-binding motifs and verify potential mimicked interactions with protein docking simulations. Both human and non-human proteins were returned for all three receptor-binding motifs. For example, all three were similar to several proteins containing EGFlike domains: some of which are endogenous to humans, such as thrombomodulin, and others exogenous, such as Plasmodium falciparum MSP-1. Similarity to human proteins may reveal which pathways the spike protein is co-opting, while analogous non-human proteins may indicate shared host interaction partners and overlapping antibody cross-reactivity. These findings can help guide experimental efforts to further understand potential interactions between human and coronavirus proteins. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

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