From infection to autoimmunity: ZnT8-mediated molecular mimicry in the triggering of post-COVID 19 type 1 diabetes mellitus

Abstract

Abstract Introduction The potential etiology of post-COVID-19 type 1 diabetes (DM1) being linked to the development of anti-Zinc Transporter 8 antibodies (ZnT8A) through molecular mimicry presents a compelling avenue for investigation, yet there remains a notable gap in our understanding of this field. While studies have revealed the presence of these autoantibodies in individuals with post-COVID-19 diabetes, the precise mechanisms by which the viral infection triggers the production of anti-ZnT8A antibodies are not yet fully comprehended. Objective To assess the molecular mimicry between the ZnT8 protein and proteins of the COVID-19 virus, as well as its potential impact on the initiation of DM1. Methods For this study, amino acid sequences of ZnT8 and COVID-19 proteins were obtained from UniProt databases. Protein structure data for ZnT8 and COVID-19 proteins were acquired from Swiss-Model. Multiple sequence alignment using VectorBuilder was performed to analyze similarities and conserved regions between the proteins. Pairwise Structure Alignment was used to assess the three-dimensional alignment of ZnT8 and COVID-19 proteins. Results The similarity results between ZnT8 and COVID-19 proteins are as follows: 1. ZnT8_HUMAN and SPIKE_SARS2: similarity of 16.67%; 2. ZnT8_HUMAN and VME1_SARS2: similarity of 26.37%; 3. ZnT8 protein and VEMP_SARS2 Envelope small membrane protein: similarity of 11.26%; and 4. ZnT8 protein and A0A883GPN5_SARS2 Nucleoprotein: similarity of 32.94%. Conclusion Based on the results obtained, it can be concluded that there is a level important of molecular mimicry between the ZnT8 protein and certain proteins of the COVID-19 virus. These findings provide insights into the potential impact of this molecular mimicry on the trigger of DM1.