Molecular Mimicry Study Between Peptides of SARS-CoV-2 and Neutrophil Extracellular Traps-Related Proteins

Abstract

Background Neutrophil extracellular traps (NETs) are observed in both COVID-19 pathology and autoimmune disorders, and molecular mimicry is a mechanism that can lead to an autoimmune response. Methods Similar sequences between SARS-CoV-2 proteins and 5 proteins (plasminogen receptor KT: PLRKT, myeloperoxidase: MPO, proteinase 3: PR-3, neutrophil elastase: NE, matrix metalloproteinase 9: MMP-9) that are present in NETs were searched. Human and SARS-CoV-2 sequence pairs were identified. Those among the identified sequence pairs, which are predicted as strong-binding peptides or epitopes of the same selected MHC class I and class II alleles, were predicted. Results In the case of MHC class I alleles, similar PLRKT and SARS-CoV-2 peptide sequences with high predicted-affinities to HLA-A*24:02, HLA-B*08:01, and HLA-B*15:01; similar MPO and SARS-CoV-2 peptide sequences with strong predicted-affinities to HLA-A*01:01, HLA-A*26:01, and HLA-B*15:01; and similar MMP-9 and SARS-CoV-2 peptide sequences with elevated predicted-affinities to HLA-B*39:01 were predicted. In the case of MHC class II alleles, similar PLRKT and SARS-CoV-2 peptide sequences with high predicted-affinities to HLA-DPA1*02:01/DPB1*01:01 were predicted. Conclusion This work is a proof-of-concept study, which revealed the potential involvement of molecular mimicry in NET pathology within susceptible individuals, in the case of being infected with SARS-CoV-2, leading to autoimmunity. © 2024 Elsevier B.V. All rights reserved.