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Article

Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins

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Department of Biological Sciences, College of Arts, Sciences and Education, Florida International University, 11200 SW 8th St, Miami, FL 33199, USA
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Bioinformatics Research Group (BioRG), Knight Foundation School of Computing and Information Sciences, Florida International University, 11200 SW 8th St, Miami, FL 33199, USA
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Department of Physics, College of Arts, Sciences and Education, Florida International University, 11200 SW 8th St, Miami, FL 33199, USA
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Machine Learning and Data Analytics Group (MLDAG), Knight Foundation School of Computing and Information Sciences, Florida International University, 11200 SW 8th St, Miami, FL 33199, USA
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Biomolecular Sciences Institute, Florida International University, 11200 SW 8th St, Miami, FL 33199, USA
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Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th St, Miami, FL 33199, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Franziska Hufsky, Alba Pérez-Cataluña, Walter Randazzo, Gloria Sanchez, Fernando González-Candelas and Manja Marz
Viruses 2022, 14(7), 1415; https://doi.org/10.3390/v14071415
Received: 30 April 2022 / Revised: 22 June 2022 / Accepted: 22 June 2022 / Published: 28 June 2022
(This article belongs to the Special Issue Virus Bioinformatics 2022)
Molecular mimicry between viral antigens and host proteins can produce cross-reacting antibodies leading to autoimmunity. The coronavirus 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. Thus, 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 high 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 involved in platelet activation and calcium regulation, and tropomyosin, which is linked to cardiac disease. 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. View Full-Text
Keywords: vaccine design; AlphaFold2; coronavirus; molecular dynamics; machine learning; protein structure comparison; COVID-19 complications; variant; omicron; tropomyosin vaccine design; AlphaFold2; coronavirus; molecular dynamics; machine learning; protein structure comparison; COVID-19 complications; variant; omicron; tropomyosin
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MDPI and ACS Style

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. Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins. Viruses 2022, 14, 1415. https://doi.org/10.3390/v14071415

AMA Style

Nunez-Castilla J, Stebliankin V, Baral P, Balbin CA, Sobhan M, Cickovski T, Mondal AM, Narasimhan G, Chapagain P, Mathee K, Siltberg-Liberles J. Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins. Viruses. 2022; 14(7):1415. https://doi.org/10.3390/v14071415

Chicago/Turabian Style

Nunez-Castilla, Janelle, Vitalii Stebliankin, Prabin Baral, Christian A. Balbin, Masrur Sobhan, Trevor Cickovski, Ananda Mohan Mondal, Giri Narasimhan, Prem Chapagain, Kalai Mathee, and Jessica Siltberg-Liberles. 2022. "Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins" Viruses 14, no. 7: 1415. https://doi.org/10.3390/v14071415

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