Journal Article

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

Balbin, Christian A., Cickovski, Trevor, Mathee, Kalai, Mondal, Ananda Mohan, Chapagain, Prem, Sobhan, Masrur, Narasimhan, Giri, Stebliankin, Vitalii, Siltberg-Liberles, Jessica, Nunez-Castilla, Janelle, Baral, Prabin

2022

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: AlphaFold2 / Amino acids / Antibodies / Antigens / Autoimmune diseases / Autoimmunity / calcium / Clotting / Coronary artery disease / coronavirus / Coronaviruses / COVID-19 / COVID-19 infection / COVID-19 vaccines / Epitopes / Health aspects / Heart diseases / humans / Infections / machine learning / Mimicry / molecular dynamics / molecular mimicry / pathogenesis / Pathogens / platelet activation / protein structure comparison / Proteins / Severe acute respiratory syndrome coronavirus 2 / Simulation / Therapeutic applications / therapeutics / Thrombocytopenia / Thrombopoietin / Tropomyosin / tropomyosins / vaccine design / Viral antigens / Viral proteins