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: Blood brain barrier; Brain; Glia; SARS-COV-2; Spike epitopes.
【저자키워드】 SARS-CoV-2, Brain, Blood brain barrier, Glia, spike epitopes, 【초록키워드】 Inflammation, observations, spike, SARS-COV-2 infection, Infection, peptide, Proteins, headache, virus, Symptoms, Toll-like receptor, Brain, Spike protein, Protein, Epitopes, peptides, death, receptor, experiment, molecular, epitope, mechanism, binding, Human brain, clinical observations, S100B, RMSD, Interaction, Hypothesis, Blood brain barrier, Glia, structures, human population, specific protein, observation, Brain infection, Loss of Smell, blurred vision, complex, epitope peptide, root, immunogenic, allele, working hypothesis, molecule, HLA-DRB1, deviation, respiratory tract illness, VCAM1, neurological abnormalities, infect, spike epitopes, TLR, zonula, zonula occludens, asphyxia, glial cell, NDRG2, selected, tested, performed, question, induce, cause, modify, the Spike, clinical observation, heterodimeric, neurological abnormality, 【제목키워드】 spike, docking, Protein, complex, TLR8, sequence, identify, heterodimeric,