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.

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

ESPOSITO, FRANCESCA;CORONA, ANGELA;GRANDI, NICOLE;PIANO, DARIO;MACCIONI, ELIAS;DISTINTO, SIMONA;TRAMONTANO, ENZO
2016

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.
Antiviral activity; Dual inhibitor; HIV-1; Plant extracts; Reverse transcriptase; Sennoside A; Medicine (all); Molecular Medicine; Pharmacology; 3003; Drug Discovery3003 Pharmaceutical Science; Complementary and Alternative Medicine2708 Dermatology
File in questo prodotto:
File Dimensione Formato  
Esposito et al Phytomedicine 2016.pdf

Solo gestori archivio

Descrizione: articolo principale
Tipologia: versione editoriale
Dimensione 1.64 MB
Formato Adobe PDF
1.64 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Esposito et al.Phytomedicine 2015.pdf

accesso aperto

Tipologia: versione pre-print
Dimensione 1.17 MB
Formato Adobe PDF
1.17 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11584/176107
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 48
  • ???jsp.display-item.citation.isi??? 44
social impact