THAA0101 | HIGH SELECTIVITY INDEX AND HIGH ANTI-HIV EFFECTS OF TWO GHANAIAN HERBAL EXTRACTS: A NEW THERAPEUTIC HORIZON

Prince Nartey¹, John Atanniba², Anthony Boateng¹, Christopher Abana¹, James Aboagye³, Helena Lamptey¹, Peter Quashie², Evelyn Yayra Bonney¹, A. George Boateng Kyei⁴ | ¹Noguchi Memorial Institute For Medical Research, Legon, Accra, Ghana; ²West African Centre for Cell Biology of Infectious Pathogens, Legon, Accra, Ghana; ³Medical and Scientific Research Centre, University of Ghana Medical Centre, Legon, Accra, Ghana; ⁴Washington University, St. Louis, USA

Despite significant advancements in antiretroviral therapy (ART), human immunodeficiency virus (HIV) remains an incurable global health burden. Despite ART's ability to suppress viral replication and reduce mortality, it necessitates lifelong adherence and faces challenges such as toxicity, cost, and resistance. Natural products offer an untapped source of antiviral compounds, having evolved for biological specificity and widely used in traditional medicine. However, their anti-HIV potential remains largely unexplored and scientifically unvalidated. This research examines the anti-HIV efficacy of two Ghanaian herbal extracts: NL001 and ODO001. Extracts were obtained using ethanolic extraction and they were freeze-dried. The cytotoxicity of these extracts was assessed using the NADPH-dependent MTT assay across U87X4 and J.Lat 10.6, as well as primary cells such as the CD4⁺ T cells from HIV-negative donors. Extract concentrations maintaining >80% cell viability (NL001: 78 µg/mL, ODO001: 0.04 mg/mL) were used to treat HIV-NL43-infected U87X4 and the CD4 T cell. The antiviral activities of these extracts were evaluated using luciferase-based assays depicting HIV-1 mRNA expression and RT-qPCR targeting cytoplasmic HIV Gag mRNA. The effects of these extracts on HIV latency and/or their post-transcriptional effects were investigated in Jurkat Latency Models (J.Lat) 10⁶ cells using flow cytometry and Gag mRNA quantification following TNF-alpha or SAHA stimulation. NL001 and ODO001 exhibited strong anti-HIV activities in the U87X4 cell line, with inhibition rates of 98.5% and 98%, respectively, and IC₅₀ values of 0.617 mg/mL and 1.04 µg/mL. The selectivity indices for these extracts exceeded 500, confirming high efficacy and minimal to no toxicity. In primary CD4⁺ T cells, both extracts achieved >70% inhibition of HIV replication. Post-transcriptional assays demonstrated substantial suppression of Gag mRNA levels: TNF-alpha + NL001 (13.8%), TNF-alpha + ODO001 (2.8%), SAHA + NL001 (0.3%), and SAHA + ODO001 (6.01%), indicating strong inhibition of HIV gene expression even following latency reversal. NL001 and ODO001 demonstrated low toxicity and high anti-HIV effects, aligning with the block-and-lock strategy. These findings highlight the potential of medicinal plants in HIV cure research, warranting further investigation and investment in plant-based therapeutic development.