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Pathog Dis. 2017 Aug 31;75(6). doi: 10.1093/femspd/ftx065.

Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.

Author information

1
Department of Life and Environmental Sciences, University of Cagliari, 09042 Monserrato, Italy.
2
Department of Pharmacy and Biotechnologies, University of Bologna, 40126 Bologna, Italy.
3
Department of Molecular Medicine, University of Padova, 35121 Padova, Italy.
4
Department of Life Sciences and Biotechnology, University of Ferrara, 44100 Ferrara, Italy.
5
Genetics and Biomedical Research institute, National Research Council (CNR), 09042 Monserrato, Cagliari, Italy.

Abstract

Despite the availability of several anti-retrovirals, there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets. Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum. It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors. Hence, here we tested the pentacyclic triterpene Lupeol, showing that it inhibits the HIV-1 RT-associated RNase H function. We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket. On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol. Results supported the potential of this plant as a valuable multitarget active drug source. In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.

KEYWORDS:

Hemidesmus indicus; Lupeol; RNase H; RT; anti-HIV-1; multitarget inhibitors; α-glucosidase

PMID:
28637198
DOI:
10.1093/femspd/ftx065
[Indexed for MEDLINE]

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