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

Beaudoin, C. A.; Jamasb, A. R.; Alsulami, A.; Copoiu, L.; van Tonder, A. J.; Hala, S.; Bannerman, B. P.; Thomas, S. E.; Vedithi, S. C.; Torres, P. H. M.; Blundell, T. L.

doi:10.1101/2021.04.23.441187

bioRxiv · 10.1101/2021.04.23.441187

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

Beaudoin, C. A.·Jamasb, A. R.·Alsulami, A.·Copoiu, L.·van Tonder, A. J.·Hala, S.·Bannerman, B. P.·Thomas, S. E.·Vedithi, S. C.·Torres, P. H. M.·Blundell, T. L.

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Abstract

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 of the virus. 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 or predicted three-dimensional protein models with the receptor-binding motifs and verify potential mimicry with protein docking simulations. Both human and non-human proteins were found to be similar to all three receptor-binding motifs. 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. HighlightsO_LIPotential coronavirus spike protein mimicry revealed by structural comparison C_LIO_LIHuman and non-human protein potential interactions with virus identified C_LIO_LIPredicted structural mimicry corroborated by protein-protein docking C_LIO_LIEpitope-based alignments may help guide vaccine efforts C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/441187v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1f09454org.highwire.dtl.DTLVardef@19a5557org.highwire.dtl.DTLVardef@158d3fdorg.highwire.dtl.DTLVardef@c59511_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Beaudoin, C. A., Jamasb, A. R., Alsulami, A., Copoiu, L., van Tonder, A. J., Hala, S., Bannerman, B. P., Thomas, S. E., Vedithi, S. C., Torres, P. H. M., Blundell, T. L.. 2021-04-26. Predicted structural mimicry of spike receptor-binding motifs from highly pathogenic human coronaviruses. https://doi.org/10.1101/2021.04.23.441187

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