Elsevier

Medical Hypotheses

Volume 157, December 2021, 110706
Medical Hypotheses

Molecular docking of SARS-COV-2 Spike epitope sequences identifies heterodimeric peptide-protein complex formation with human Zo-1, TLR8 and brain specific glial proteins

https://doi.org/10.1016/j.mehy.2021.110706Get rights and content

Highlights

  • Spike epitope forms heterodimeric complex with Zonula Occluden.

  • Spike epitope forms heterodimeric complex with VCAM.

  • Spike epitope forms heterodimeric complex with astrocyte protein NDRG2.

  • Spike epitope forms heterodimeric complex with glial protein Apo S100B.

  • Spike epitopes (1–60 and 241–300) binds with HLA-DRB1 alleles.

Abstract

SARS-COV-2 infection causes severe respiratory tract illness leading to asphyxia and death. The onset of infection is associated with loss of smell, blurred vision, headache with bronchopulmonary symptoms. The clinical observations of neurological abnormalities lead us to address the question, does the virus enter into brain and what is the underlying mechanism of brain infection? The working hypothesis is, SARS-COV-2 Spike epitopes modify blood brain barrier and infect glial cells to induce brain inflammation in genetically diverse human population. The hypothesis is tested by determining binding or interacting ability of virus Spike epitope peptides M1Lys60 and Ala240Glu300 with human toll-like receptor 8 (TLR 8), brain targeted Vascular Cell adhesion Molecules (VCAM1) proteins, Zonula Occludens (ZO), glial cell specific protein NDRG2 and Apo- S100B. The molecular dynamic experiments are performed, and root mean square deviation (RMSD) values are determined for interactions between the Spike peptides and selected proteins. The observations demonstrate formation of heterodimeric complex between the epitope peptides and selected protein structures. The viral epitopes have ability to bind with HLA-DRB1 15:01, 07:01 or 03.01 alleles thus found immunogenic in nature. The observations altogether suggest entry of these Spike protein epitopes into human brain causes inflammation.

Keywords

Spike epitopes
SARS-COV-2
Glia
Blood brain barrier
Brain

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