PropertyValue
?:abstract
  • Currently, more than 33 million peoples have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than a million people died from coronavirus disease 2019 (COVID-19), a disease caused by the virus. There have been multiple reports of autoimmune and inflammatory diseases following SARS-CoV-2 infections. There are several suggested mechanisms involved in the development of autoimmune diseases, including cross-reactivity (molecular mimicry). A typical workflow for discovering cross-reactive epitopes (mimotopes) starts with a sequence similarity search between protein sequences of human and a pathogen. However, sequence similarity information alone is not enough to predict cross-reactivity between proteins since proteins can share highly similar conformational epitopes whose amino acid residues are situated far apart in the linear protein sequences. Therefore, we used a hidden Markov model-based tool to identify distant viral homologs of human proteins. Also, we utilized experimentally determined and modeled protein structures of SARS-CoV-2 and human proteins to find homologous protein structures between them. Next, we predicted binding affinity (IC50) of potentially cross-reactive T-cell epitopes to 34 MHC allelic variants that have been associated with autoimmune diseases using multiple prediction algorithms. Overall, from 8,138 SARS-CoV-2 genomes, we identified 3,238 potentially cross-reactive B-cell epitopes covering six human proteins and 1,224 potentially cross-reactive T-cell epitopes covering 285 human proteins. To visualize the predicted cross-reactive T-cell and B-cell epitopes, we developed a web-based application “Molecular Mimicry Map (3M) of SARS-CoV-2” (available at https://ahs2202.github.io/3M/). The web application enables researchers to explore potential cross-reactive SARS-CoV-2 epitopes alongside custom peptide vaccines, allowing researchers to identify potentially suboptimal peptide vaccine candidates or less ideal part of a whole virus vaccine to design a safer vaccine for people with genetic and environmental predispositions to autoimmune diseases. Together, the computational resources and the interactive web application provide a foundation for the investigation of molecular mimicry in the pathogenesis of autoimmune disease following COVID-19.
is ?:annotates of
?:creator
?:doi
?:doi
  • 10.1101/2020.11.12.344424
?:externalLink
?:journal
  • bioRxiv
?:license
  • biorxiv
?:pdf_json_files
  • document_parses/pdf_json/930a369d3b11b169c37a3be3b304791ce84c6818.json
?:publication_isRelatedTo_Disease
is ?:relation_isRelatedTo_publication of
?:sha_id
?:source
  • BioRxiv; WHO
?:title
  • Molecular Mimicry Map (3M) of SARS-CoV-2: Prediction of potentially immunopathogenic SARS-CoV-2 epitopes via a novel immunoinformatic approach
?:type
?:year
  • 2020-11-12

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