In Silico binding of human immunodeficiency virus (HIV) with STRA6 could explain the mystery of the immunodeficiency caused by HIV infection. An exciting breakthrough in molecular docking and Virology
Authors: Elkazzaz Mahmoud , Haikal Abdullah , Shamkh Israa M , Ahmed Amr 
Published: November 2022

Abstract
Great strides have been made to reduce the number of human immunodeficiency virus (HIV) infections and HIV/acquired immunodeficiency syndrome (AIDS)-related deaths, but the war against HIV is far from over. From 1981 to the present, human immunodeficiency virus, the etiological agent of AIDS, has unwaveringly killed an estimated 39 million individuals. Although, the chemokine receptor CCR5 is the predominant co-receptor exploited for transmission and replication of HIV in vivo but our docking analysis, predicted and discovered a novel receptor termed STRA 6 that may play a critical role in the pathogenicity of HIV and its immune suppression. According to our breakthrough HIV may bind to STRA6 which is a receptor of Retinol /Vitamin A leading to retinol in sufficiency, immune dysregulation and hyper inflammation. Therefore, it is not surprising that Vitamin A deficiency is common in people with HIV infection. 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. It is well established that vitamin A supplementation improves growth and reduces morbidity in HIV-infected children. RA which is the active metabolite of Vitamin A is produced by gut-associated dendritic cells, which are among the first cells encountered by HIV. Acute HIV infection results in rapid reduction of RA levels and dysregulation of immune cell populations whose identities and function are largely controlled by RA. Surprisingly, our molecular docking based analysis showed that spike protein receptor Binding Domain (RDB) of HIV strongly and efficiently binds to STRA6 receptor, definitely to the RDB vital residues of RBP-binding motif located in STRA 6 receptor. In this study, the STRA 6 – HIV was examined in order to describe the mechanism of the viral protein's interaction with the various patient symptoms and see the reaction's features for the first time, which may be employed as a therapeutic option. The interaction between the viral protein and the STRA 6 is created here for detection and to identify the mode of action of the mechanism, and the proteins of the HIV and STRA 6 receptor were generated and docked using the HDOCK server. The binding pocket of the STRA 6-HIV protein complexes docking score is -334.71 kcal/mol, according to the surface aspect of the complex. The results of the MD simulations revealed the significant stability of the spike protein with the STRA6 up to 100 ns.
Conclusion
STRA 6 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, HIV Spike protein exhibited high docking score with human STRA 6 with low binding energy. According to our HIV could bind to the cytosolic part of the cellular membrane via binding to STRA6 leading to lead to deformation of the cytosolic membrane and inserting its viral particles into the cell also, our findings demonstrate that vitamin A supplements, retinoic acid and STRA6 induction will be promising and effective treatments for HIV infection and its unknown etiology symptoms. This study paves the way towards understanding the complex mechanism of HIV infection and its immune dysregulation, and may lead to the discovery of new drug targets for HIV. In vitro studies involving genetic engineering or gene knockdown of the STRA6 are needed to further investigate the role of these receptors in HIV pathogenesis.