Potential autoimmunity resulting from molecular mimicry between SARS-CoV-2 Spike and human proteins

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 invest...

Full description

Saved in:
Bibliographic Details
Published in:bioRxiv 2022-02
Main Authors: Nunez-Castilla, Janelle, Stebliankin, Vitalii, Baral, Prabin, Balbin, Christian A, Sobhan, Masrur, Cickovski, Trevor, Mondal, Ananda M, Narasimhan, Giri, Chapagain, Prem, Mathee, Kalai, Siltberg-Liberles, Jessica
Format: Article
Language:English
Subjects:
Antibodies
Computer applications
Coronaviruses
COVID-19
Cross-reactivity
Epitopes
Mimicry
Pandemics
Platelets
Proteins
Severe acute respiratory syndrome coronavirus 2
Spike protein
Thrombocytopenia
Thrombopoietin
Citations: Items that cite this one
Online Access:Request full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Competing Interest Statement The authors have declared no competing interest. Footnotes * The manuscript has been extended from focusing on one molecular mimic to include all molecular mimics from SARS-CoV-2 Spike based on PDB ID 6XR8 and Epitopedia.
DOI:10.1101/2021.08.10.455737