Figure 1. MuSIC strategy. Multiplex screening for interacting compounds (MuSIC) technology is able to identify synergistic drug pairs. The technology involves distributing 1,000 approved or clinically tested drugs [a] into an arrayed compound library. An algorithm [b]
ensures each of the possible 500,000 interactions between two given molecules is represented in 13,106 pools [c]. The pools in the primary arrayed compound library are evaluated for activity against HIV-infected cells [d]. Hits (red wells) from the primary screen are evaluated, and identified synergistic pairs are used to construct a secondary arrayed compound library, which also is evaluated for antiviral activity [e]. Hits (red wells) from the secondary library are validated using concentration titrations of the two drugs [f]. The analyses of antiviral efficacy for steps [d] and [e] involved a two-part cell-based assay that measured effects of molecules on early and later stages of the virus' lifecycle.