Systematic identification of synergistic drug pairs targeting HIV.
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.
Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Xu
X
Tan
Long
L
Hu
Lovelace J
LJ
Luquette
Geng
G
Gao
Yifang
Y
Liu
Hongjing
H
Qu
Ruibin
R
Xi
Zhi John
ZJ
Lu
Peter J
PJ
Park
Stephen J
SJ
Elledge
D000465:Algorithms; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004357:Drug Synergism; D006678:HIV / Q000187:drug effects* / Q000502:physiology*; D006801:Humans
D019380:Anti-HIV Agents