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Abstract Title:

Sennoside A, derived from the traditional chinese medicine plant Rheum L., is a new dual HIV-1 inhibitor effective on HIV-1 replication.

Abstract Source:

Phytomedicine. 2016 Nov 15 ;23(12):1383-1391. Epub 2016 Aug 10. PMID: 27765358

Abstract Author(s):

Francesca Esposito, Ilaria Carli, Claudia Del Vecchio, Lijia Xu, Angela Corona, Nicole Grandi, Dario Piano, Elias Maccioni, Simona Distinto, Cristina Parolin, Enzo Tramontano

Article Affiliation:

Francesca Esposito

Abstract:

BACKGROUND: Despite the availability of effective antiretroviral therapies, drugs for HIV-1 treatment with new mode of action are still needed. An innovative approach is aimed to identify dual HIV-1 inhibitors, small molecules that can inhibit two viral functions at the same time. Rhubarb, originated from Rheum palmatum L. and Rheum officinale Baill., is one of the earliest and most commonly used medicinal plants in Traditional Chinese Medicine (TCM) practice. We wanted to explore TCM for the identification of new chemical scaffolds with dual action abilities against HIV-1.

METHODS: R. palmatum L. and R. officinale Baill. extracts along with their main single isolated constituents anthraquinone derivatives were tested on both HIV-1 Reverse Transcriptase (RT)-associated DNA Polymerase (RDDP) and Ribonuclease H (RNase H) activities in biochemical assays. Active compounds were then assayed for their effects on HIV-1 mutated RTs, integrase (IN) and viral replication.

RESULTS: Both R. palmatum L. and R. officinale Baill. extracts inhibited the HIV-1 RT-associated RNase H activity. Among the isolated constituents, Sennoside A and B were effective on both RDDP and RNase H RT-associated functions in biochemical assays. Sennoside A was less potent when tested on K103N, Y181C, Y188L, N474A and Q475A mutated RTs, suggesting the involvement of two RT binding sites for its antiviral activity. Sennoside A affected also HIV-1 IN activity in vitro and HIV-1 replication in cell-based assays. Viral DNA production and time of addition studies showed that Sennoside A targets the HIV-1 reverse transcription process.

CONCLUSION: Sennoside A is a new scaffold for the development of HIV-1 dual RT inhibitors.

Study Type : In Vitro Study

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Sayer Ji
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