FIGURE 3.

High-throughput screening to identify specific agents targeting nucleocytoplasmic transport that have antiviral activity. High-throughput screening strategies to rapidly identify antiviral compounds that specifically block viral:IMP/XPO/host protein interaction. (i) Primary screening is performed using a chemical library to identify molecules that inhibit viral protein-IMP/XPO interaction. (ii) Hits are counterscreened to identify compounds that target IMP/XPO function directly, which although of interest for research applications, are discarded from further examination in the pipeline toward specific antivirals. (iii) Compounds not targeting IMP/XPO function but rather specifically inhibiting viral protein:IMP/XPO interaction are screened in cell-based assays (iv) to confirm antiviral activity. (v) Structure-activity relationship analysis/focused library screening) is performed to optimize properties of the inhibitor (e.g., pharmacodynamics) in multiple iterations (vi), prior to evaluation of lead compounds in animal models of viral infection (vii).