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Updated: May 17, 2026

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
Published on: May 21, 2018
Systematic identification of synergistic drug pairs targeting HIV
Xu Tan1, Long Hu, Lovelace J Luquette
1Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Abstract:
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.
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