Resource type
Date created
2015
Authors/Contributors
Author: Tietjen, Ian
Author: Ntie-Kang, Fidele
Author: Mwimanzi, Philip
Author: Onguéné, Pascal Amoa
Author: Scull, Margaret A.
Author: Idowu, Thomas Oyebode
Author: Ogundaini, Abiodun Oguntuga
Author: Meva’a, Luc Mbaze
Author: Abegaz, Berhanu M.
Author: Rice, Charles M.
Author: Andrae-Marobela, Kerstin
Author: Brockman, Mark A.
Author: Brumme, Zabrina L.
Author: Fedida, David
Abstract
The continued burden of HIV in resource-limited regions such as parts of sub-Saharan Africa, combined with adverse effects and potential risks of resistance to existing antiretroviral therapies, emphasize the need to identify new HIV inhibitors. Here we performed a virtual screen of molecules from the pan-African Natural Product Library, the largest collection of medicinal plant-derived pure compounds on the African continent. We identified eight molecules with structural similarity to reported interactors of Vpu, an HIV-1 accessory protein with reported ion channel activity. Using in vitro HIV-1 replication assays with a CD4+ T cell line and peripheral blood mononuclear cells, we confirmed antiviral activity and minimal cytotoxicity for two compounds, ixoratannin A-2 and boldine. Notably, ixoratannin A-2 retained inhibitory activity against recombinant HIV-1 strains encoding patient-derived mutations that confer resistance to protease, non-nucleoside reverse transcriptase, or integrase inhibitors. Moreover, ixoratannin A-2 was less effective at inhibiting replication of HIV-1 lacking Vpu, supporting this protein as a possible direct or indirect target. In contrast, boldine was less effective against a protease inhibitor-resistant HIV-1 strain. Both ixoratannin A-2 and boldine also inhibited in vitro replication of hepatitis C virus (HCV). However, BIT-225, a previously-reported Vpu inhibitor, demonstrated antiviral activity but also cytotoxicity in HIV-1 and HCV replication assays. Our work identifies pure compounds derived from African plants with potential novel activities against viruses that disproportionately afflict resource-limited regions of the world.
Document
Published as
Tietjen I, Ntie-Kang F, Mwimanzi P, Onguéné PA, Scull MA, Idowu TO, et al. (2015) Screening of the Pan-African Natural Product Library Identifies Ixoratannin A-2 and Boldine as Novel HIV-1 Inhibitors. PLoS ONE 10(4): e0121099. doi:10.1371/journal.pone.0121099
Publication details
Publication title
PLoS ONE
Document title
Screening of the Pan-African Natural Product Library Identifies Ixoratannin A-2 and Boldine as Novel HIV-1 Inhibitors
Date
2015
Volume
10
Issue
4
Publisher DOI
10.1371/journal.pone.0121099
Rights (standard)
Copyright statement
Copyright is held by the author(s).
Scholarly level
Peer reviewed?
Yes
Funder
Funder: Grand Challenges Canada
Language
English
Member of collection
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journal.pone_.0121099.pdf | 2.72 MB |