Abstract
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.
Keywords: AlphaFold2; COVID-19 complications; coronavirus; machine learning; molecular dynamics; omicron; protein structure comparison; tropomyosin; vaccine design; variant.
【저자키워드】 coronavirus, machine learning, Vaccine design, molecular dynamics, omicron, COVID-19 complications, Variant., AlphaFold2, protein structure comparison, tropomyosin, 【초록키워드】 COVID-19, SARS-CoV-2, Autoimmunity, platelet activation, Vaccine, coronavirus, spike, antibody, machine learning, Vaccine design, variant, Symptom, molecular dynamics, omicron, coronavirus SARS-CoV-2, COVID-19 complications, Adverse reactions, outcomes, Protein, Epitopes, Antibody binding, Viral, COVID-19 pathogenesis, Asymptomatic, protein structure, Autoimmune, thrombocytopenia, molecular, molecular mimicry, cardiac disease, disease, calcium, COVID-19 patients, SARS-CoV-2 spike, tropomyosin, host proteins, cross-reacting antibodies, Thrombopoietin, Viral antigen, Regulation, viral antigens, human proteins, host protein, therapeutic interventions, therapeutic intervention, explanation, disorder, motif, hotspot, implication, highlight, PRKG1, resulting, example, involved, investigated, induce, cause, reduce, COVID-19 complication, 【제목키워드】 SARS-CoV-2, spike, Human, mimicry, Potential,