2025/01/01 by Imran Zafar, Zain Abbas, Sidra Abbas +4 · 1 voice · 1 citation
Immunology and Microbiology · Medicine · Biochemistry, Genetics and Molecular Biology · #HIV Research and Treatment #HIV/AIDS drug development and treatment #Transgenic Plants and Applications
paper · doi:10.1515/chem-2025-0130
openalex publication_date 2025/01/01 · openalex created_date 2025/03/13 · openalex updated_date 2026/06/14
Abstract This study investigates the potential of alkaloids – nitidine, harmine, harmaline, berberine, and magnoflurine – as inhibitors of HIV –CD4 binding, focusing on their molecular interactions, binding affinities, and pharmacokinetic properties. Molecular docking results revealed that all alkaloids exhibited high-affinity binding to the CD4 receptor and showed significant interactions with the HIV spike protein ( HIV -SP). Interaction analysis showed that nitidine and harmaline formed hydrogen bonds and hydrophobic interactions, while harmine and magnoflurine relied on van der Waals forces and π-stacking. Pharmacokinetic evaluations, based on Lipinski’s Rule of Five, showed that nitidine and magnoflurine exhibited favorable oral bioavailability, moderate lipophilicity, and blood–brain barrier permeability, with nitidine having a bioavailability score of 0.55, and showing promising candidate for the development of anti- HIV therapeutics, supported by their binding solid affinities, stability in MD simulations, and favorable pharmacokinetic profiles. MD simulations confirmed the stability of the CD4– HIV -SP complex, with magnesium fluoride showing the highest strength and minimal structural deviation, while nitidine and berberine exhibited binding solid stability. MM-GBSA calculations confirmed magnesium fluoride as the most potent inhibitor with the highest binding free energy.