Abstract
Background
A global pandemic of pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, at the end of 2019. Although, the ACE2 receptor has been demonstrated to be the main entry receptor of COVID-19, but our docking analysis, predicted and discovered a novel receptor termed STRA6 that may play a critical role in the pathogenicity of COVID-19 and explain the common pre and post COVID-19 symptoms with unknown etiology. STRA6 receptor expressed in many organs and immune cells, upregulated by retinoic acid jm6 (STRA6) was the first protein to be identified in a novel category of proteins, cytokine signaling transporters, due to its ability to function as both a cell surface receptor and a membrane protein that binds to retinol binding protein facilitating cellular uptake of retinol. The primary ligand of STRA6 (vitamin/retinol) was shown to be drastically reduced during COVID-19 infection, which agrees with our findings.
Methods
The STRA6 receptor protein were submitted to the server for functional interaction associated network between partners for the STRING (Research Online of Interacting Genes/Proteins Data Basis version 10.0)13 .Docking study of each Spike -ACE 2 and STRA6 receptor protein were carried out using HDOCK server (http://hdock.phys.hust.edu.cn/). The binding mode of Spike -ACE 2 and STRA6 receptor protein is retrieved form the PDB https://www.rcsb.org/ with accession number (7DMU, 5sy1)
Results
Surprisingly, our molecular docking based analysis showed that spike protein Receptor Binding Domain(RDB) of COVID-19 strongly and efficiently binds to STRA6 receptor, definitely to the RDB vital residues of RBP-binding motif located in STRA6 receptor. STRA6 receptor is a membrane receptor responsible for signaling and transporting of Vitamin A(Retinol) from plasma retinol binding protein (RBP) to our cells. In an outstanding manner, COVID-19 Spike protein exhibited high docking score with human STRA6 with low binding energy. The docking score of COVID-19 spike protein was stronger than the docking score of spike protein with ACE2.The surface view of complex reveals that the binding pocket of STRA6- Spike protein and Spike ACE 2 complexes with RMSD (189.44 Å, 1.00 Å ) representatively and docking score (-341.21 ,-354.68) kcal/mol the quality of the receptor and the ligand are LGscore and MaxSub ( 2.416, 0.147 ). The spike to bind to RDB of the STRA 6 protein in the ILE 131C, MET 145C, HIS 86A with interface residue( 4.961, 4.953 and 3.271) representatively.
In conclusion
STRA6 mutations results in a broad spectrum of complication related to malformations including congenital heart defects, anophthalmia, alveolar capillary dysplasia, diaphragmatic hernia, lung hypoplasia and mental retardation. Moreover, Retinoic acid metabolism is defective in COVID-19 (cytokine storm), sepsis, ARDS and SIRS. Therefore, we believe that this novel discovery that STRA6 receptor acts as a novel binding receptor for COVID-19 will shed new light on effective treatments against COVID-19 and may explain many pre and post-covid-91 symptoms with unknown etiology. Therefore, reconstitution of the signaling of retinoid may prove to be a valid strategy for COVID-19 management. According to our findings Vitamin A supplements and retinoic acid will be promising and effective treatments for COVID-19 infection and its unknown aetiology symptoms. it worth mentioning that aerosolized all- trans retinoic acid is currently under clinical investigation (ClinicalTrials.gov Identifier: NCT05002530)
The distribution of cellular retinoic acid binding protein(CRABP) in the central nervous system of the chick embryo during the development.
