Molecular Docking Evaluation of Mangiferin against HIV1 Reverse Transcriptase Ani Riani Hasana (a*), Naufa Hanif (a), Binar Pratama (a)
Department of Pharmacy, Faculty of Health Sciences, Universitas Jenderal Soedirman
Jalan Dr. Soeparno, Kampus Karangwangkal, Purwokerto 53123, Indonesia
*ani.riani[at]unsoed.ac.id
Abstract
Human Immunodeficiency Virus type-1 (HIV-1) remains one of the most pressing global health challenges, particularly due to the emergence of antiretroviral drug resistance that limits long-term treatment effectiveness. Reverse transcriptase (RT) is a key enzyme in the viral replication cycle, responsible for converting viral RNA into proviral DNA, making it an essential target for therapeutic intervention. Mangiferin, the major C-glucosyl xanthone from Mangifera indica L., has been reported to exhibit broad-spectrum antiviral activity and potential interactions with viral enzymes. Nevertheless, its specific molecular interactions with HIV-1 RT remain poorly understood. This study aims to evaluate the binding affinity of mangiferin toward two functional sites of RT: the non-nucleoside inhibitor binding pocket (NNIBP) and the RNase H domain. Molecular docking was performed using high-resolution crystal structures of RT (PDB IDs: 1FK9 for NNIBP and 3QIO for RNase H). Validation of the docking protocol was conducted through redocking of reference ligands, efavirenz for NNIBP and a raltegravir derivative for RNase H, to ensure reliability of the method. Binding free energy (Δ-G), hydrogen bonding patterns, and hydrophobic interactions were analyzed to characterize ligand-protein interactions. The expected outcomes include identification of stable binding conformations and favorable energy scores of mangiferin with RT functional sites. These results may provide preliminary evidence supporting mangiferin as a promising natural compound for development as an HIV-1 RT inhibitor, warranting further in vitro and in vivo investigations.
