Systematic identification of synergistic drug pairs targeting HIV.

Citation:

Tan X, Hu L, Luquette LJ, Gao G, Liu Y, Qu H, Xi R, Lu ZJ, Park PJ, Elledge SJ. Systematic identification of synergistic drug pairs targeting HIV. Nat Biotechnol 2012;30(11):1125-30. Copy at http://www.tinyurl.com/y6yu43xt

Date Published:

2012 Nov

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.

Last updated on 10/19/2015