Molecular Mimicry of SARS-CoV-2 Spike Protein in the Nervous System: A Bioinformatics Approach

The 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.

To 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.

A 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.

A 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.

Proteins 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.