Molecular mimicry between human and microbial/viral/parasite peptides is common and has long been associated with the etiology of autoimmune disorders provoked by exogenous pathogens. A growing body of evidence accumulated in recent years suggests a strong correlation between SARS-CoV-2 infection and autoimmunity. The article analyzes the immunogenic potential of the peptides shared between the SARS-CoV-2 spike glycoprotein (S-protein) and antigens of human endocrinocytes involved in most common autoimmune endocrinopathies. A total of 14 pentapeptides shared by the SARS-CoV-2 S-protein, thyroid, pituitary, adrenal cortex autoantigens and beta-cells of the islets of Langerhans were identified, all of them belong to the immunoreactive epitopes of SARS-CoV-2. The discussion of the findings relates the results to the clinical correlates of COVID-19-associated autoimmune endocrinopathies. The most common of these illnesses is an autoimmune thyroid disease, so the majority of shared pentapeptides belong to the marker autoantigens of this disease. The most important in pathogenesis of severe COVID-19, according to the authors, may be autoimmunity against adrenals because their adequate response prevents excessive systemic action of the inflammatory mediators causing cytokine storm and hemodynamic shock. A critique of the antigenic mimicry concept is given with an assertion that peptide sharing is not a guarantee but only a prerequisite for provoking autoimmunity based on the molecular mimicry. The latter event occurs in carriers of certain HLA haplotypes and when a shared peptide is only used in antigen processing

In post-COVID-19 syndrome, clinical presentation of the nerve fiber dysfunction plays an important role. The possibility of autoantigen cross-mimicry of coronavirus infection and the peripheral nervous system need to be investigated. The bioinformatic analysis was applied to search for possible common protein sequences located in the immunological epitopes. Among the autoantigens of the human nervous system, fibroblast growth factor receptor protein 3, myelin protein P0, myelin protein P2, sodium channel protein type 9, alpha protein subunit, plexin-D1 protein and ubiquitin-carboxyl-terminal hydrolase protein of the L1 isoenzyme were selected. The “Alignmentaj” program was created. The UniProt database, Protein Data Bank and AlphaFold databases were used. The analysis of protein sequence similarities of spike glycoproteins in human coronaviruses revealed common pentapeptides of the MERS-CoV-2 virus with the fibroblast growth factor receptor 3 and myelin protein P2. Among seasonal coronaviruses, common peptide sequences were identified in HCoV-HKU-1 virus with sodium channel protein type 9 subunit alpha and Plexin-D1, HCoV-OС43 with Plexin-D1, as well as HCoV-NL63 with Plexin-D1 and Ubiquitin carboxyl-terminal hydrolase isozyme L1. The data obtained make it possible to identify new potential targets for the development of autoimmune reactions that occur against the background of the activity of highly pathogenic and seasonal coronaviruses.

Molecular mimicry between human and microbial/viral/parasite peptides is common and for a long time is associated with the etiology of autoimmune disorders provoked by exogenous pathogens. Increasing evidence accumulated from the past years suggests a strong correlation between the SARS-CoV-2 infection and autoimmunity. The article analyzes the immunogenic potential of the peptides shared between SARS-CoV-2 spike glycoprotein (S-protein and antigens of human endocrinocytes involved in most common autoimmune endocrinopathies. Totally the study revealed 14 pentapeptides shared by S-protein of SARS-CoV-2 and autoantigens of thyroid, pituitary, adrenal cortex and Langerhans’ islets beta-cells, 12 of them belong to immunoreactive epitopes of SARS-CoV-2. The discussion of the data links the results with clinical correlates of COVID-associated autoimmune endocrinopathies. Most common of them is an autoimmune thyroid disease, so the majority of shared pentapeptides belong to marker autoantigens of this disease. Most important in pathogenesis of severe COVID-19, according authors’ opinion, can be autoimmunity against adrenals, because their adequate response prevents from excessive systemic action of inflammatory mediators which cause cytokine storm and hemodynamic shock. The criticism of antigen mimicry concept is given with a statement that peptide sharing is not a guarantee, but just a prerequisite of autoimmunity excess provocation. The last event occurs in carriers of certain HLA haplotypes and in case when shared peptide is used in antigen processing only [1 figure, 5 tables, bibliography 38 references].

The article is devoted to the problem of autoimmune diseases provocation by coronavirus infection and the role of molecular mimicry in this phenomenon. SARS-CoV-2 can disguise its proteins as human ones in order to avoid immune attack. A bioinformatics analysis of the probable pentapeptide sharing between human autoantigens of endocrinocytes and SARS-CoV-2 spike protein, membrane protein and nucleocapsid protein was performed. Antigen mimicry between S-proteins of all other known human Coronaviruses and typical target autoantigens of endocrinocytes was also explored. Six human-identical regions were found in the SARS-CoV-2 membrane and nucleocapsid proteins, all of them in their immunodominant epitopes. All shared epitopes belong to antigens of endocrine cells commonly targeted during autoimmune endocrinopathies. Moreover, samples of the pituitary, adrenal and thyroid from patients who died from coronovirus infection (COVID-19) were studied morphologically using histochemical methods. A high frequency of SARS-CoV-2 caused inflammation of the studied endocrine organs was found in patients who died from severe COVID-19. At the same time, the abundant expression of virus antigens by the cells of the adenohypophysis was combined with the complete absence of its expression by the cells of the neurohypophysis. SARS-CoV-2 infected cells apparently perished by non-apoptotic pathway. The foci of lesions in endocrine organs contained abundant lymphocytic infiltrates which may witness for the impact of autoimmune processes. The facts revealed emphasize the need of endocrinological diagnostic alertness of a physician while observing patients with post-vaccination and post-COVID-19 health disorders. [3 figures, 6 tables, bibliography: 45 references].

In order to identify corresponding amino acid sequences (pentapeptides) between the SPs, MPs and NPs of human coronaviruses and human autoantigens targeted in autoimmune endocrinopathies, and for a comparative analysis of the various coronaviruses proteome and the proteome of human, the original computer program was used. Quantitatively, SP, MP and NP of the human coronaviruses were found to share totally 117 minimal immune pentapeptide epitopes: 79 in SP, 14 in MP and 24 in NP, – with 18 autoantigens expressed by human endocrinocytes. The shared pentapeptides belong to the proteins of human endocrine cells. Samples of the pituitary, adrenal and thyroid from patients who died from coronavirus infection (COVID-19) were studied morphologically using histochemical methods. A high incidence of SARS-CoV-2 infection of endocrine cells was showed. The high affinity of SARS-CoV-2 the cells of the adenohypophysis was revealed, but there was no expression of viral proteins by the cells of the neurohypophysis. The foci of lesions in endocrine organs contained abundant lymphocytic infiltrates which may indicate the impact of autoimmune processes. Autoimmune disorders have a multi-faceted etiology and depend on polygenic predispose and additive action of many epigenetic and environmental factors causing hyperstimulation of imperfectly functioning immune system. It means that the phenomenon of molecular mimicry cannot be blamed as their single prerequisite, but it is just a tile in mosaic of autoimmunity. The facts revealed emphasize the need of endocrinological diagnostic alertness of a physician while observing patients with post-vaccination and post-COVID-19 health disorders.