Anti-HIV-1 activity of quinic acid isolated from Helichrysum mimetes using NMR-based metabolomics and computational analysis

Abstract

Helichrysum species are widely used in traditional medicine with potential against infectious diseases. Extraction of the aerial parts of 32 Helichrysum species was done using polar (methanol:water (1:1)) and non-polar (hexane, dichloromethane and acetone) solvent systems. Anti-human immunodeficiency virus (HIV) bioassays revealed that polar extracts of H. mimetes and H. chrysargyrum (2.5 μg/mL), polar and non-polar extracts of H. cephaloideum (25 μg/mL) and polar and non-polar extracts of H. zeyheri, H. setosum, H. platypterum and H. kraussii at (2.5 μg/mL), had greater than 90% inhibitory activity. The polar extract of H. mimetes (100 μg/mL) exhibited 55.93% reverse transcriptase (RT) inhibition as a possible indication of the mechanism of action. Proton NMR spectra of the polar extracts exhibited the presence of aromatic compounds and carbohydrate moieties. Principal component analysis (PCA) of the polar extracts showed clustering related to the activity of the extracts with good predictability scores (Q2 > 0.5). However, orthogonal projections to latent structures discriminant analysis (OPLS-DA) predictability of the model was low based on the Q2 at approximately 0.25. Quinic acid (QA) isolated from H. mimetes showed promising anti-RT activity (IC50 = 53.82 μg/mL) comparable to the positive drug control, doxorubicin (IC50 = 40.31 μg/mL). A molecular docking study revealed the probable binding site and conformation of QA within cavity 4, with a docking score of − 8.03. The docking score of doxorubicin within cavity 4 was − 7.87. These are the first reports of QA's HIV-1-RT activity, as well as doxorubicin's docking characteristics on this enzyme.