In silico Discovering STRA 6 Vitamin A Receptor, as a Novel Binding Receptor of COVID-19

Abstract: 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 STRA 6 that may play a critical role in the pathogenicity of COVID-19. STRA6 receptor expressed in many organs and immune cells, upregulated by retinoic acid jm6 (STRA 6) 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. We analyze the STRA6 and ACE2 receptor networks to predict the specific association among certain other proteins which might rely on similar functionality. Molecular docking showed a high affinity between the Spike protein with STRA6, the docking score of COVID-19 spike protein with STRA6 (-354.68) kcal/mol was higher than the docking score of spike protein with ACE2 (-341.21) kcal/mol. Results of MD simulations revealed significant stability of the spike protein with STRA6 up to 100 ns. SARS-CoV-2 spike protein binds strongly and directly to STRA6. Which are highly expressed in Lymphatic system and Immune cells. This study paves the way towards understanding the complex mechanism of existing of covid-19 infection complications such as immune suppression and ineffective RIG-I pathway. Restoring the balance between the STRA6 and ACE2 in the context of spike protein RBD may be promising target in SARS CoV-2 Pathogenesis and may reveal new drug targets for new variants of COVID-19. Keywords: COVID-19, STRA6, ACE2, Molecular docking.