Molecular mimicry between Spike and human thrombopoietin may induce thrombocytopenia in COVID-19

Nunez-Castilla, J.; Stebliankin, V.; Baral, P.; Balbin, C. A.; Sobhan, M.; Cickovski, T.; Mondal, A. M.; Narasimhan, G.; Chapagain, P.; Mathee, K.; Siltberg-Liberles, J.

doi:10.1101/2021.08.10.455737

bioRxiv · 10.1101/2021.08.10.455737

Molecular mimicry between Spike and human thrombopoietin may induce thrombocytopenia in COVID-19

Nunez-Castilla, J.·Stebliankin, V.·Baral, P.·Balbin, C. A.·Sobhan, M.·Cickovski, T.·Mondal, A. M.·Narasimhan, G.·Chapagain, P.·Mathee, K.·Siltberg-Liberles, J.

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Abstract

SARS-CoV-2 causes COVID-19, a disease curiously resulting in varied symptoms and outcomes, ranging from asymptomatic to fatal. Autoimmunity due to cross-reacting antibodies resulting from molecular mimicry between viral antigens and host proteins may provide an explanation. We computationally investigated molecular mimicry between SARS-CoV-2 Spike and known epitopes. We discovered molecular mimicry hotspots in Spike and highlight two examples with tentative autoimmune potential and implications for understanding COVID-19 complications. We show that a TQLPP motif in Spike and thrombopoietin shares similar antibody binding properties. Antibodies cross-reacting with thrombopoietin may induce thrombocytopenia, a condition observed in COVID-19 patients. Another motif, ELDKY, is shared in multiple human proteins such as PRKG1 and tropomyosin. Antibodies cross-reacting with PRKG1 and tropomyosin may cause known COVID-19 complications such as blood-clotting disorders and cardiac disease, respectively. Our findings illuminate COVID-19 pathogenesis and highlight the importance of considering autoimmune potential when developing therapeutic interventions to reduce adverse reactions.

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Nunez-Castilla, J., Stebliankin, V., Baral, P., Balbin, C. A., Sobhan, M., Cickovski, T., Mondal, A. M., Narasimhan, G., Chapagain, P., Mathee, K., Siltberg-Liberles, J.. 2021-08-11. Molecular mimicry between Spike and human thrombopoietin may induce thrombocytopenia in COVID-19. https://doi.org/10.1101/2021.08.10.455737

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