Exploration of plant alkaloids as potential inhibitors of HIV –CD4 binding: Insight into comprehensive in silico approaches

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.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Exploration of plant alkaloids as potential inhibitors of HIV –CD4 binding: Insight into comprehensive in silico approaches ; volume:23 ; number:1 ; year:2025 ; extent:18 ; Open chemistry ; 23, Heft 1 (2025) (gesamt 18)

Contributors, Places and Time

• Creator: Zafar, Imran ; Abbas, Zain ; Abbas, Sidra ; Odimayo, Oluwagbade Joseph ; Ain, Qurat ul ; Dawoud, Turki M. ; Mahamat, Ousman B.

Further information

• DOI: 10.1515/chem-2025-0130
• URN: urn:nbn:de:101:1-2503130254241.473682515732
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:23 AM CEST