STRA6 (vitamin A receptor), as a Novel binding receptor of COVID-19 (A breakthrough)
Mahmoud Elkazzaz, Tamer Haydara, Yousry Esam-Eldin Abo-Amer, Israa M Shamkh, Mohammed . F Abo El Magd, Amr Ahmed
doi:10.21203/rs.3.rs-892203/v3
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 rst protein to be identi ed 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 ndings.
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 e ciently binds to STRA6 receptor, de nitely 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..
Declarations Con ict of Interest Statement The author declares that the research was conducted in the absence of any commercial or nancial relationships that could be construed as a potential con ict of interest. The spike to bind to RD8 of the STRA 6 protein
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'abstract': '<jats:p>The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 '
'(SARS-CoV-2) has infected over 100 million people causing over 2.4 million deaths over the '
'world, and it is still expanding. Given the urgency of the COVID-19 pandemic, the clinical '
'investigation of approved drugs is a promising alternative to find a timely effective '
'treatment. In this randomized trial, we investigated the activity of both oral and '
'aerosolized 13 cis retinoic acid in the treatment of SARS-COV-2 added to standard of care '
'treatment in patients with COVID-19 versus standard of care treatment alone. This was a '
'randomized controlled trial conducted at Kafrelsheikh Universitys Quarantine Hospitals, '
'Egypt. After obtaining informed consent, forty patients with a confirmed diagnosis of '
'COVID-19 were enrolled in the study. They were randomly assigned to one of two groups: Group '
'I; 20 patients received aerosolized and oral 13 cis retinoic acid plus standard of care '
'treatment (13 cis RA group) and Group II; 20 patients received only standard care treatment '
'as a control group. The two groups were age and gender matched. There was no statistically '
'significant difference between them in any of the baseline characteristics or laboratory '
'parameters. The results showed that there was a high significant difference between the two '
'groups regarding intensive care unit (ICU) admission, mortality and improvement '
'(P<0.05). Only 10.52 % of patients in the 13 cis retinoic acid group needed ICU '
'admission compared to 28.57 % in the control arm. There was no mortality in the 13 cis '
'retinoic acid group, whereas about 14.35% were died in the group II. All patients who '
'received 13 cis retinoic acid noticed a high improvement (P<0.001), and the mean value for '
'clinical improvement was 16 days. There was no significant difference regarding the '
'laboratory parameters before and after 14 days of treatment in the group of patients received '
'the standard of care treatment (P=0.66). Univariate logistic regression analysis showed '
'overall mortality was significantly related to the patients age, serum ferritin, C-reactive '
'protein, oxygen saturation, the presence of diabetes mellitus, obesity, and abdominal pain. '
'We conclude that 13 cis retinoic acid is a promising drug in the treatment of patients '
'with COVID-19 infection, when added to the standard of care treatment.</jats:p>',
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'title': ['13 cis retinoic acid improved the outcomes of COVID-19 patients. A randomized clinical trial'],
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