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10.1371/journal.pone.0121099

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suck abstract from ncbi


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pmid25830320
      PLoS+One 2015 ; 10 (4 ): e0121099
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  • Screening of the Pan-African natural product library identifies ixoratannin A-2 and boldine as novel HIV-1 inhibitors #MMPMID25830320
  • Tietjen I ; Ntie-Kang F ; Mwimanzi P ; Onguéné PA ; Scull MA ; Idowu TO ; Ogundaini AO ; Meva'a LM ; Abegaz BM ; Rice CM ; Andrae-Marobela K ; Brockman MA ; Brumme ZL ; Fedida D
  • PLoS One 2015[]; 10 (4 ): e0121099 PMID25830320 show ga
  • 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.
  • |Aporphines/chemistry/*pharmacology [MESH]
  • |Biological Products/*chemistry [MESH]
  • |CD4-Positive T-Lymphocytes/cytology/virology [MESH]
  • |Cell Line [MESH]
  • |Drug Resistance, Viral [MESH]
  • |Guanidines/pharmacology [MESH]
  • |HIV-1/*drug effects/physiology [MESH]
  • |Hepacivirus/drug effects/physiology [MESH]
  • |Human Immunodeficiency Virus Proteins/antagonists & inhibitors/metabolism [MESH]
  • |Humans [MESH]
  • |Leukocytes, Mononuclear/cytology/virology [MESH]
  • |Molecular Docking Simulation [MESH]
  • |Proanthocyanidins/chemistry/*pharmacology [MESH]
  • |Pyrazoles/pharmacology [MESH]
  • |Viral Regulatory and Accessory Proteins/antagonists & inhibitors/metabolism [MESH]


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