Systematic identification of synergistic drug pairs targeting HIV
Open Access
- 14 October 2012
- journal article
- research article
- Published by Springer Nature in Nature Biotechnology
- Vol. 30 (11), 1125-1130
- https://doi.org/10.1038/nbt.2391
Abstract
Tan et al. use a multiplex screening method to systematically evaluate ∼500,000 drug pairs assembled from a collection of 1,000 FDA-approved or clinically tested compounds, and identify drugs that synergize to inhibit HIV replication. The systematic identification of effective drug combinations has been hindered by the unavailability of methods that can explore the large combinatorial search space of drug interactions. Here we present multiplex screening for interacting compounds (MuSIC), which expedites the comprehensive assessment of pairwise compound interactions. We examined ∼500,000 drug pairs from 1,000 US Food and Drug Administration (FDA)-approved or clinically tested drugs and identified drugs that synergize to inhibit HIV replication. Our analysis reveals an enrichment of anti-inflammatory drugs in drug combinations that synergize against HIV. As inflammation accompanies HIV infection, these findings indicate that inhibiting inflammation could curb HIV propagation. Multiple drug pairs identified in this study, including various glucocorticoids and nitazoxanide (NTZ), synergize by targeting different steps in the HIV life cycle. MuSIC can be applied to a wide variety of disease-relevant screens to facilitate efficient identification of compound combinations.Keywords
This publication has 40 references indexed in Scilit:
- Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression MechanismsJournal of Virology, 2011
- Cytoscape 2.8: new features for data integration and network visualizationBioinformatics, 2010
- Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in WomenScience, 2010
- Thiazolides, a New Class of Anti-influenza Molecules Targeting Viral Hemagglutinin at the Post-translational LevelJournal of Biological Chemistry, 2009
- Synergistic drug combinations tend to improve therapeutically relevant selectivityNature Biotechnology, 2009
- Combination Therapy in Treatment of Experimental Pulmonary Aspergillosis: In Vitro and In Vivo Correlations of the Concentration- and Dose- Dependent Interactions between Anidulafungin and Voriconazole by Bliss Independence Drug Interaction AnalysisAntimicrobial Agents and Chemotherapy, 2009
- The Challenge of Finding a Cure for HIV InfectionScience, 2009
- Identification of Host Proteins Required for HIV Infection Through a Functional Genomic ScreenScience, 2008
- Relationship between T Cell Activation and CD4+T Cell Count in HIV‐Seropositive Individuals with Undetectable Plasma HIV RNA Levels in the Absence of TherapyThe Journal of Infectious Diseases, 2008
- Functional classification of drugs by properties of their pairwise interactionsNature Genetics, 2006