Design of Small Molecules with HIV Fusion Inhibitory Property Based on Gp41 Interaction Assay

Background: Gp41 of HIV (Human Immunodeficiency Virus) is a protein that mediates fusion between viral and cellular membranes. The agent, T-20, which has been approved for HIV inhibition, can restrain Gp41 function in the fusion process; nevertheless, it has disadvantages like instability, high cost of production and injection form to be delivered twice a day. Methods: Several molecules like NB-2 and NB-64 have been discovered that can inhibit HIV infection. These molecules were used as template compounds to design and develop more effective small molecules functioning as HIV-1 fu-sion inhibitors targeting Gp41. The process included in silico docking protocols using HEX and ArgusLab applications. A multisource database was created, after choosing the best molecules; they were tested in vitro for inhibitory ac-tivity by HIV-1 single-cycle model, transfected in HEK cells (293T). Results: Computational analysis and experimental data were combined to explore molecular properties and the most potent ones were found, with th