Ying-Shan Han1, Wei-Lie Xiao2, Hongtao Xu1, Victor G Kramer1, Yudong Quan1, Thibault Mesplède1, Maureen Oliveira1, Susan P Colby-Germinario1, Han-Dong Sun2, Mark A Wainberg3. 1. McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada. 2. State Key Laboratory of Phytochemistry and Plant Resource in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China. 3. McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada mark.wainberg@mcgill.ca.
Abstract
BACKGROUND: Due to resistance to all classes of anti-HIV drugs and drug toxicity, there is a need for the discovery and development of new anti-HIV drugs. METHODS: HIV-1 inhibitors were identified and biologically characterized for mechanism of action. RESULTS: We identified a dibenzocyclooctadiene lignan, termed HDS2 that possessed anti-HIV activity against a wide variety of viral strains with EC50 values in the 1-3 µM range. HDS2 was shown to act as an NNRTI by qPCR and in vitro enzyme assays. CONCLUSIONS: This compound provides a new scaffold for further optimization of activity through structure-guided design.
BACKGROUND: Due to resistance to all classes of anti-HIV drugs and drug toxicity, there is a need for the discovery and development of new anti-HIV drugs. METHODS:HIV-1 inhibitors were identified and biologically characterized for mechanism of action. RESULTS: We identified a dibenzocyclooctadiene lignan, termed HDS2 that possessed anti-HIV activity against a wide variety of viral strains with EC50 values in the 1-3 µM range. HDS2 was shown to act as an NNRTI by qPCR and in vitro enzyme assays. CONCLUSIONS: This compound provides a new scaffold for further optimization of activity through structure-guided design.
Authors: Kamalendra Singh; Bruno Marchand; Devendra K Rai; Bechan Sharma; Eleftherios Michailidis; Emily M Ryan; Kayla B Matzek; Maxwell D Leslie; Ariel N Hagedorn; Zhe Li; Pieter R Norden; Atsuko Hachiya; Michael A Parniak; Hong-Tao Xu; Mark A Wainberg; Stefan G Sarafianos Journal: J Biol Chem Date: 2012-09-06 Impact factor: 5.157
Authors: Javier P Martinez; Bettina Hinkelmann; Eric Fleta-Soriano; Heinrich Steinmetz; Rolf Jansen; Juana Diez; Ronald Frank; Florenz Sasse; Andreas Meyerhans Journal: Microb Cell Fact Date: 2013-09-24 Impact factor: 5.328