In Silico Study of Molecular Mimicry Between Sars-Cov and Neutrophil Extracellular Traps Composition in Granulocyte-Rich Supernatants of Patients With Systemic Lupus Erythematosus and Lupus Nephritis

Abstract

Neutrophil extracellular traps (NETs) are detected in both COVID-19 and autoimmune disorders. Molecular mimicry between NETs-related proteins and SARS-CoV-2 proteins may be the mechanism that can lead to an autoimmune response. Accordingly, similar sequences were searched with blastp, between SARS-CoV-2 proteins and 148 proteins that were reported in the NETs composition induced in neutrophils of supernatants from patients with systemic lupus erythematosus and lupus nephritis. Query-subject epitope pairs with strong-binding affinities to 12 HLA supertype representative alleles were predicted for the aligned sequences with at least 50% identities. According to the prediction results, all HLA alleles under study have affinities to the similar SARS-CoV-2 and NETs' proteins. These affinities can bring molecular mimicry-based autoimmunity risk with NETs-pathology, in susceptible individuals, upon infection with SARS-CoV-2. However, HLA-A∗01:01 carriers can be at a higher risk due to the association of this allele with the highest number of NETs-related human proteins, and similar (unique) query-subject epitope pairs of those proteins and SARS-CoV-2. Additionally, HLA-A∗02:01 carriers may specifically be prone to higher risk than expected, if infected with SARS-CoV-2. Furthermore, HLA-A∗24:02 was predicted to bind strongly to an elevated number of unique SARS-CoV-2 subject sequences while the number of both associated human proteins, and unique queries of those, are rather low. It may be indicative of a pertaining pathology despite viral evolution. © 2023 Elsevier Inc. All rights reserved.