GHP-88309 (GHP88309) is a non-nucleoside, broad-spectrum allosteric inhibitor of paramyxovirus polymerase with EC50 of 0.9 uM against HPIV3-JS RdRP.Demonstrates highly potent antiviral potency against HPIV3-JS and clinical isolates HPIV3-9R4 and HPIV3-10L3 in the primary cell/virus isolate system (EC50=0.07-0.08 uM), without cytotoxicity.GHP-88309 targets a conserved microdomain in the L protein, inhibiting de novo RNA synthesis.GHP-88309 is efficacious in well-differentiated human airway epithelium cultures grown at air-liquid interface (3D-ALI-HBTEC).GHP-88309 (150 mg/kg b.i.d.) is orally efficacious in HPIV disease surrogate model.GHP-88309 possesses unusual broad-spectrum activity against diverse paramyxoviruses including respiroviruses (i.e. HPIV1 and HPIV3) and morbilliviruses (i.e. MeV).
