Chemical diversity and activity profiles of HIV-1 reverse transcriptase inhibitors from plants

TLDR: The chemical diversity and activity profiles of HIV-1 reverse transcriptase inhibitors from plants reveal two recurring motifs: the structure of several active anti- Reverse transcriptase compounds mimics nucleoside analogues, and numerous anti-reverse transcriptase phytochemicals have pleiotropic effects and heterogenous pharmacological benefits during infection and disease.

Abstract: Current challenges to antiretroviral therapy have opened new vistas in the search for novel drugs from natural products. This review focusses on plants as sources of inhibitors for human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. Based on a systematic search of the literature, anti-HIV-1 reverse transcriptase activity was recorded for 132 plant species in 100 genera and 51 families. Seven families comprise 52.6% of plant species with anti-reverse transcriptase activity: Lamiaceae (13.7%), Fabaceae (10.7%), Euphorbiaceae (9.9%), Clusiaceae (6.1%), Asteraceae (4.6%), Combretaceae (4.6%), and Moraceae (3.0%). The repertoire of anti-reverse transcriptase active compounds includes (-)-catechin, 1,8-cineole, 3,4-di-O-caffeoylquinic acid, 5,7-dimethoxy-6-methylflavone, apigenin, baicalein, betulinic acid, caffeic acid, cis-3-hexene-1-ol, eugenol, euscaphic acid, gallic acid, hoslunddiol, limonene, naringenin, oleanolic acid, p-cymene, pomolic acid, quinic acid, rosmarinic acid, stigmasterol, thymol, ursolic acid, α-bergamotene, α-pinene, and γ-terpinene. Among the IC50 values are 0.10 μg/ml (Uvaria angolensis), 3 μg/ml (Hemidesmus indicus), 2. 3μg/ml (Adansonia digitata), 6.24 μg/ml (Caesalpinia coriaria), 7.2 μg/ml (Terminalia sericea), 17.4 μg/ml (Hypoxis hemerocallidea), and 79 μg/ml (Moringa oleifera). The chemical diversity and activity profiles of HIV-1 reverse transcriptase inhibitors from plants reveal two recurring motifs: the structure of several active anti-reverse transcriptase compounds mimics nucleoside analogues, and numerous anti-reverse transcriptase phytochemicals have pleiotropic effects and heterogenous pharmacological benefits during infection and disease. To accelerate drug discovery and development, this review recommends the urgent need to tap into the rich vein of indigenous knowledge of putative anti-HIV/AIDS medicinal plants (reverse pharmacology), determine pan-assay interference compounds, analyze structure-activity relationships, and conduct more clinical trials.