Structure-activity relationship, molecular docking, and molecular dynamic studies of diterpenes from marine natural products with anti-HIV activity

HIV-1 infection is a global epidemic whose treatment is limited majorly by viral resistance and adverse effects. Natural products from algae have been studied for many years, including antiviral, being an alternative to anti-HIV drug design. Since the isolation of natural products can be a hurdle, molecular modeling is an important tool to study these compounds. Herein, structure-activity relationship, molecular docking, and molecular dynamic studies were performed to direct the studies of ten marine natural products with anti-HIV activity. In the structure-activity relationship, descriptors were identified associating the anti-HIV activity of five diterpenes with possible action on the reverse transcriptase allosteric site. These diterpenes were evaluated by molecular docking, and it was identified that only dolabelladienetriol interacted in the allosteric site. Molecular dynamics suggested that the dolabelladienetriol might interfere with the viral RNA binding to HIV-1 RT by inducing a conformational change of the enzyme. Also, in silico ADMET simulations predicts that the dolabelladienetriol present a high potential to be successfully developed as a drug. Thus, applying in silico approaches was possible to suggest potential anti-HIV compounds derived from marine natural products. Communicated by Ramaswamy H. Sarma

Automated summary

In this study, molecular modeling techniques were used to investigate marine natural products with anti-HIV activity. The results suggest that dolabelladienetriol may have the potential to be developed as an effective antiretroviral drug, based on its interaction with the allosteric site of HIV-1 reverse transcriptase and its ability to induce conformational changes in the enzyme. The in silico ADMET simulations also support the promising prospects of dolabelladienetriol as a drug candidate.