Bibliographic Details
| Title: |
Screening of the Pan-African natural product library identifies ixoratannin A-2 and boldine as novel HIV-1 inhibitors. |
| Authors: |
Ian Tietjen, Fidele Ntie-Kang, Philip Mwimanzi, Pascal Amoa Onguéné, Margaret A Scull, Thomas Oyebode Idowu, Abiodun Oguntuga Ogundaini, Luc Mbaze Meva'a, Berhanu M Abegaz, Charles M Rice, Kerstin Andrae-Marobela, Mark A Brockman, Zabrina L Brumme, David Fedida |
| Source: |
PLoS ONE, Vol 10, Iss 4, p e0121099 (2015) |
| Publisher Information: |
Public Library of Science (PLoS), 2015. |
| Publication Year: |
2015 |
| Collection: |
LCC:Medicine
LCC:Science |
| Subject Terms: |
Medicine, Science |
| More Details: |
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 Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1932-6203 |
| Relation: |
http://europepmc.org/articles/PMC4382154?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: |
10.1371/journal.pone.0121099 |
| Access URL: |
https://doaj.org/article/b91ee5438af0424b8ce2e79377ca7d95 |
| Accession Number: |
edsdoj.b91ee5438af0424b8ce2e79377ca7d95 |
| Database: |
Directory of Open Access Journals |
