Abstract :
Although antiretroviral therapy (ART) has been significantly successful, HIV-1 remains incurable due to persistent viral reservoirs, chronic immune dysregulation, and drug resistance, necessitating the discovery of novel multi-target therapeutics. Euclea spp., a medicinal plant widely used in Southern African traditional medicine, possesses diverse bioactive phytochemicals with reported antimicrobial and immunomodulatory properties; however, its anti-HIV potential remains poorly understood. This study integrated network pharmacology, molecular docking, phytochemical profiling, and in vitro assays to investigate the anti-HIV activity of Euclea spp. Sixteen phytochemicals satisfying Lipinski’s Rule of Five and exhibiting favorable pharmacokinetic properties were identified and mapped to 313 human targets. Enrichment analyses revealed significant modulation of pathways implicated in HIV persistence and immune dysfunction, including Th17 cell differentiation, IL-17, PD-1/PD-L1, HIF-1, and PI3K-Akt signaling. Crude extracts were fractionated using solvents of increasing polarity (hexane, dichloromethane, ethyl acetate, ethanol, and water), and a traditional concoction was prepared and profiled using GC-MS and LC-MS. All fractions exhibited low cytotoxicity in TZM-bl and HEK293 cells (CC₅₀ >300 μg/mL). Ethyl acetate, ethanol, aqueous fractions, and the traditional concoction demonstrated potent antiviral activity (IC₅₀ <5 μg/mL), whereas hexane and dichloromethane fractions exhibited moderate activity (IC₅₀ >10 μg/mL). Time-of-addition assays indicated potent inhibition at multiple stages of the HIV replication cycle, supported by molecular docking, which demonstrated favorable binding affinities toward key HIV targets. Collectively, these findings provide the first comprehensive evidence that Euclea spp. possess multi-target anti-HIV activity and highlight traditional medicinal plants as promising sources of next-generation adjunctive HIV therapeutics.
Biography:
Ernest Oduro-Kwateng is a PhD student in the HIV Pathogenesis Programme (HPP), University of KwaZulu-Natal (UKZN), South Africa. His research focuses on computational bioinformatics, natural product–based therapeutics, and molecular models of HIV pathogenesis. He employs integrative approaches, including systems pharmacology, molecular modeling, mechanistic HIV assays, and innovative formulation strategies, to identify novel therapeutic strategies targeting HIV persistence and immune dysfunction. He has authored peer-reviewed publications on HIV latency, immunomodulation, mechanistic HIV research, and computational drug discovery. His broader interests include host-directed therapies, nanotechnology-based drug delivery systems, and the translational development of natural products for treating infectious diseases.
