1Department of Pharmaceutical Chemistry, K.B. Raval College of Pharmacy, Gandhinagar, Gujarat, India, 382423.
2a,2bDepartment of Pharmaceutics, Shree Swaminarayan Sanskar Pharmacy College, Zundal Gandhinagar, Gujarat, India, 382421.
2c,3a,3bDepartment of Pharmaceutical Chemistry, Swaminarayan University, Kalol, Gandhinagar, Gujarat, India, 382725.
3cDepartment of Pharmaceutical Chemistry, Institute of Pharmacy, Gandhinagar University, Khatraj Gandhinagar, Gujarat, India, 382721.
3dDepartment of Pharmaceutical Chemistry, Sal Institute of Pharmacy, Ahmedabad, Gujarat, India, 380060.
Introduction: Human immunodeficiency virus type-1 (HIV-1) replication depends on the coordinated activity of viral enzymes, particularly reverse transcriptase and protease, which are critical for genome replication and viral maturation. Targeting these enzymes remains a central strategy in antiviral drug development.
Materials and Methods: In the present study, an integrated in silico–in vitro approach was employed to investigate plant-derived phytochemicals as potential inhibitors of HIV-1 reverse transcriptase and protease. Molecular docking was performed to predict binding affinities and interaction patterns of selected phytochemicals with the catalytic regions of both enzymes. Drug-likeness and pharmacokinetic properties were evaluated using ADMET and SwissADME tools, while biological activity was predicted using PASS analysis.
Results and Discussion: Experimental validation was carried out using enzyme-based inhibition assays, complemented by cytotoxicity assessment in host cells using the MTT assay. Docking analyses revealed stable and target-specific interactions of phytochemicals with key amino acid residues involved in enzyme activity. In vitro assays confirmed inhibitory effects with IC₅₀ values ranging from 2.0 to 30.0 μM, alongside acceptable cytotoxicity profiles. Several compounds demonstrated differential inhibition of reverse transcriptase and protease, indicating distinct modes of interference with HIV-1 replication machinery.
Conclusion: Overall, this study provides mechanistic insight into the inhibition of HIV-1 enzymes by structurally diverse phytochemicals and establishes a direct correlation between predicted molecular interactions and functional enzyme inhibition. The findings highlight the potential of natural compounds as lead scaffolds for structure-guided antiviral drug development targeting HIV-1 pathogenesis.
Keywords: Anti-HIV phytochemicals, HIV-1 protease, reverse transcriptase, drug-likeness, Lipinski's Rule of Five, bioinformatics, Phyto-HIV Database, natural product-based drug discovery.
How to cite this article: Kotadiya M, Lakhani R, Trivedi D, Prajapati R, Patel R, Vyas N, Chavda H, Patel MS. Mechanistic In Silico and In Vitro Evaluation of Phytochemicals Targeting HIV-1 Reverse Transcriptase and Protease. Int J Drug Deliv Technol. 2026;16(15s): 658-673. DOI: 10.25258/ijddt.16.15s.76
Source of support: Nil.
Conflict of interest: None