EMoMiS: A pipeline for epitope-based molecular mimicry search in protein structures with potential applications to SARS-CoV-2

The Epitope-based Molecular Mimicry Search (EMoMiS) pipeline developed in this study provides a valuable computational tool for predicting molecular mimicry between antigens. The novelty of the tool includes a prediction of antibody cross-reactivity, which can have beneficial or detrimental effects on the immune system. The developed pipeline can be seen as a tool for pandemic preparedness. First, EMoMiS can predict if antibodies produced by exposure to prior viruses can cross-react with a newly emerged pathogen, resulting in cross-protection. On the other hand, EMoMiS can suggest if molecular mimicry between a pathogen and human proteins can lead to autoimmune disorders, such that early preventive therapeutics strategies can be developed. After we first verified that EMoMiS could predict previously documented cross-reactivity between antibodies for the Zika virus with Dengue, the pipeline predicted examples of molecular mimicry between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike and other proteins, including thrombopoietin (TPO), a hormone that regulates systemic platelet concentrations. The study provides experimental support for the predicted molecular mimicry by showing increased TPO co-localization with platelets, complement-fixing IgM antibodies, and C3d in lung tissue sections from SARS-CoV-2 patients.