Targeting the HIV-1 Tat and Human Tat Protein Complex through Natural Products: An In Silico Docking and Molecular Dynamics Simulation Approach

Background: Tat protein is considered essential for substantial HIV-1 replication, and is also required to break HIV-1 latency, resulting in productive HIV replication. The multifaceted regulatory role of HIV Tat and the fact that it is expressed in the early stages of HIV infection justify its potential as an anti-HIV drug target. Objective: The present study was undertaken with the aim to target HIV-1 Tat protein with natural compounds which could help in identifying potential inhibitors against HIV-1 Tat. Methods: In this study, we compared the binding of Tat protein and Human P-TEFb Tat protein complex (TPC) with phyto-steroids and terpenes to evaluate their potential for HIV-1 treatment. The docking ability of plant products with HIV-1 Tat and TPC was studied with respect to dissociation constant, geometric shape complementary score, approximate interface area, and binding energy using Patch dock and YASARA. Molecular dynamics simulation was set up to investigate the interactions of the natural compounds with Tat protein and human tat protein complex (TPC). Results: The binding energy and dissociation constant of Diosgenin, Catharanthine and Ginkgolide A with Tat and TPC were comparable to antiretroviral drugs, Maraviroc and Emtricitabine. The natural products, Diosgenin, Ginkgolide A and Catharanthine, showed the highest binding energy and were stable with Tat protein and TPC in the entire MD simulation run. Conclusion: The natural products, Diosgenin, Ginkgolide A and Catharanthine, showed highest binding energy and were stable with Tat protein and TPC in the entire MD simulation run. The binding energy and dissociation constant of Diosgenin, Catharanthine and Ginkgolide A with Tat and TPC were comparable to antiretroviral drugs, Maraviroc and Emtricitabine.