In-silico identification of phytochemical compounds from various medicinal plants as potent HIV-1 non-nucleoside reverse transcriptase inhibitors utilizing molecular docking and molecular dynamics simulations

Suleiman Danladi; Ayinde Abdulwahab Adeniyi; Zainab Iman Sani; Adegbenro Temitope

doi:10.1093/biomethods/bpaf081

In-silico identification of phytochemical compounds from various medicinal plants as potent HIV-1 non-nucleoside reverse transcriptase inhibitors utilizing molecular docking and molecular dynamics simulations

Biol Methods Protoc. 2025 Nov 12;10(1):bpaf081. doi: 10.1093/biomethods/bpaf081. eCollection 2025.

Authors

Suleiman Danladi¹, Ayinde Abdulwahab Adeniyi¹, Zainab Iman Sani¹, Adegbenro Temitope²

Affiliations

¹ Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Bayero University, Kano 700006, Nigeria.
² Faculty of Pharmacy, University of Lagos, Lagos 101017, Nigeria.

Abstract

HIV is a global public health challenge. The Reverse Transcriptase (RT) enzyme facilitates an important step in HIV replication. Inhibition of this enzyme provides a critical target for HIV treatment. The aim of this study is to employ computational techniques to screen bioactive compounds from different medicinal plants toward identifying potent HIV-1 RT inhibitors better activity than the current ones. We conducted a literature review of HIV-1 RT inhibitors, and eighty-four (84) compounds, while target receptor (1REV) was retrieved from Protein Data Bank. The molecular docking and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) evaluations were performed using the Maestro Schrodinger software user interface. The drug-likeness and pharmacokinetic profile evaluation were carried out using SwissADME and ADMETlab3.0 web servers. Lastly, molecular dynamics simulation study was conducted using the Desmond tool of Schrodinger. The molecular docking study revealed that Rosmarinic acid (-13.265 kcal/mol), Evafirenz/standard drug (-12.175 kcal/mol), Arctigenin (-11.322 kcal/mol), Luteolin (-11.274 kcal/mol), Anolignan A (-11.157 kcal/mol), and Quercetin (-11.129 kcal/mol) can effectively bind with high affinity and low energy values to the HIV-1 RT enzyme. The relative binding free energies of Rosmarinic acid, Evafirenz, Arctigenin, Luteolin, Anolignan A, and Quercetin were -66.85, -66.53, -51.83, -49.77, -58.17, and -49.62 Δg bind, respectively. The ADMET profile of Arctigenin was similar to that of Efavirenz, and better than that of other top compounds. The molecular dynamics simulation study showed better stability of rosmarinic acid with the active site of HIV-1 NNRT than the cocrystalized ligand. Out of the top five compounds identified in this study, Rosmarinic acid, a current inhibitor of HIV-1 RT in vitro, showed the most promising prediction. However, further in vivo studies and human clinical trials are required to provide more concrete information regarding its efficacy as potent HIV-1 RT inhibitors.

Keywords: HIV-1; MMGBSA; NNRTI; molecular docking; molecular dynamics.