Molecular docking and molecular dynamics simulation to predict inhibitors against HIV envelope 1 protein

Abstract

HIV (human immunodeficiency virus) is a virus that attacks the immune system, which serves as the body’s defense mechanism. If untreated, HIV can lead to AIDS (acquired immunodeficiency syndrome), which raises risk for a host of problems, especially infections and cancers. According to data from 2022, there are 39 million people worldwide affected with HIV. HIV remains a leading cause of death glob- ally, although AIDS-related deaths have declined due to ART (antiretroviral therapy). There are two main types of HIV viruses: HIV-1 and HIV-2. HIV-1 is more prevalent worldwide, while HIV-2 is less pathogenic and found predominantly in Africa. Although not fully understood, the key differences between HIV-1 and HIV-2 viruses lie in the mechanism of retroviral pathogenesis. On the surface of the HIV-1 virus, there is a protein called the envelope protein that facilitates viral entry into host cells by mediating the fusion of the viral membrane with the host cell membrane. In our work, we have used computational strategies like molecular docking and molecular dynamics simulations to predict inhibitors that can bind to the envelope protein, thus inhibiting viral entry into the host cell. We hypothesize that the docked ligands bind strongly to the Phe43 cavity and prevent the CD4 receptor from binding the viral HT1 protein. Preventing the HT1-CD4 proteins’ interaction will prevent the HIV and human cell from binding. Based on our studies, we have proposed five chemical compounds that bind strongly to the viral envelope protein. These chemical compounds bind specifically to the Phe43 cavity on the envelope protein. The Phe43 cavity is a promising target for drug therapy. We have also introduced virtual reality (VR) technology to visualize the protein-ligand complexes. Our current work will not only help in developing novel therapeutics against HIV, but also pave the way for many potential new treatments, thus helping combat the global burden of this disease.

Keywords: HIV (human immunodeficiency virus), HT1-CD4 proteins, AIDS (acquired immunodeficiency syndrome).