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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.
Pubmed ID: 25830320 RIS Download
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Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsNIAID research strives to understand, treat, and ultimately prevent the myriad infectious, immunologic, and allergic diseases that threaten millions of human lives. Major areas of investigation: * Acquired Immunodeficiency Syndrome (AIDS) * Asthma and Allergic Diseases * Biodefense * Emerging and Re-emerging Infectious Diseases * Enteric Diseases * Fundamental Immunology * Genetics and Transplantation * Immune-Mediated Diseases * Influenza * Pathogen Genomics * Sexually Transmitted Infections (STIs) * Vaccine Development * Drug Research and Development * Antimicrobial Resistance * Minority and Women''s Health
View all literature mentionsThe Canadian Institutes of Health Research (CIHR) is the Government of Canada''s agency responsible for funding health research in Canada. CIHR was created in 2000 under the authority of the CIHR Act and reports to Parliament through the Minister of Health. CIHR''s budget for 2008-09 is $928.6 million, of which $132 million is allocated to administering the Networks of Centres of Excellence and Canada Research Chair programs. CIHR was created to transform health research in Canada by: * funding more research on targeted priority areas; * building research capacity in under-developed areas such as population health and health services research; * training the next generation of health researchers; and * focusing on knowledge translation, so that the results of research are transformed into policies, practices, procedures, products and services. CIHR consists of 13 virtual institutes, a structure that is unique in the world. These innovative institutes bring together all partners in the research process - the people who fund research, those who carry it out and those who use its results - to share ideas and focus on what Canadians need: good health and the means to prevent disease and fight it when it happens. Each institute supports a broad spectrum of research in its topic areas and, in consultation with its stakeholders, sets priorities for research in those areas.
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View all literature mentionsNIH HIV Reagent Program has been managed under contract by American Type Culture Collection (ATCC) since 2020. ATCC shall maintain the NIH HIV Reagent Program through identification, acquisition, production, receipt, storage, maintenance, distribution and disposal of biological and chemical research organisms and materials for HIV and other infectious diseases for use in basic and translational research.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Huh-7.5 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Huh-7.5.1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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