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Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins.

ABSTRACT: Molecular mimicry between viral antigens and host proteins can produce cross-reacting antibodies leading to autoimmunity. The coronavirus SARS-CoV-2 causes COVID-19, a disease curiously resulting in varied symptoms and outcomes, ranging from asymptomatic to fatal. Autoimmunity due to cross-reacting antibodies resulting from molecular mimicry between viral antigens and host proteins may provide an explanation. Thus, we computationally investigated molecular mimicry between SARS-CoV-2 Spike and known epitopes. We discovered molecular mimicry hotspots in Spike and highlight two examples with tentative high autoimmune potential and implications for understanding COVID-19 complications. We show that a TQLPP motif in Spike and thrombopoietin shares similar antibody binding properties. Antibodies cross-reacting with thrombopoietin may induce thrombocytopenia, a condition observed in COVID-19 patients. Another motif, ELDKY, is shared in multiple human proteins, such as PRKG1 involved in platelet activation and calcium regulation, and tropomyosin, which is linked to cardiac disease. Antibodies cross-reacting with PRKG1 and tropomyosin may cause known COVID-19 complications such as blood-clotting disorders and cardiac disease, respectively. Our findings illuminate COVID-19 pathogenesis and highlight the importance of considering autoimmune potential when developing therapeutic interventions to reduce adverse reactions.

SUBMITTER: Nunez-Castilla J

PROVIDER: S-EPMC9318917 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThe development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in record time to cope with the ongoing coronavirus disease 2019 (COVID-19) pandemic has led to uncertainty about their use and the appearance of adverse neurological reactions. The SARS-CoV-2 spike protein (SP) is used to produce neutralizing antibodies and stimulate innate immunity. However, considering the alterations in the nervous system (NS) caused by COVID- 19, cross-reactions are plausible.ObjectiveTo identify peptides in Homo sapiens SP-like proteins involved in myelin and axon homeostasis that may be affected due to molecular mimicry by antibodies and T cells induced by interaction with SP.Materials and methodsA bioinformatics approach was used. To select the H. sapiens proteins to be studied, related biological processes categorized based on gene ontology were extracted through the construction of a protein-protein interaction network. Peripheral myelin protein 22, a major component of myelin in the peripheral nervous system, was used as the query protein. The extracellular domains and regions susceptible to recognition by antibodies were extracted from UniProt. In the study of T cells, linear sequence similarity between H. sapiens proteins and SP was assessed using BLASTp. This study considered the similarity in terms of biochemical groups per residue and affinity to the human major histocompatibility complex (human leukocyte antigen I), which were evaluated using Needle and NetMHCpan 4.1, respectively.ResultsA large number of shared pentapeptides between SP and H. sapiens proteins were identified. However, only a small group of 39 proteins was linked to axon and myelin homeostasis. In particular, some proteins, such as phosphacan, attractin, and teneurin-4, were susceptible targets of B and T cells. Other proteins closely related to myelin components in the NS, such as myelin-associated glycoprotein, were found to share at least one pentamer with SP in extracellular domains.ConclusionProteins involved in the maintenance of nerve conduction in the central and peripheral NS were identified in H. sapiens. Based on these findings, re-evaluation of the vaccine composition is recommended to prevent possible neurological side effects.

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Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins.

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