GHP-88309 is an orally available non-nucleoside paramyxovirus polymerase inhibitor with broad-spectrum anti-paramyxoviral activity (EC50 in μM= 0.4/HPIV3-JS, 0.8/HPIV3-5F6, 2/SeV-F1R-eGF, 0.6/MeV/Alaska.USA 16.00, 0.4/CDV-5804p) and little cytoxicity (CC50 >20μM). GHP-88309 potently inhibits the replication of HPIV1 isolate 5F6 and HPIV3 isolates 10L3 & 9R4 in 3D-ALI-HBTEC human airway organoids (EC50 = 280,90, 105 nM, respectively) in 3D-ALI-HBTECs. HPIV3 and provides complete protection against lethal Sendai virus infection in mice (150 mg/kg bid. po. starting at time of infection or 48 hrs after), a murine surrogate model of human HPIV3 disease.
Orally available non-nucleoside paramyxovirus polymerase inhibitor with broad-spectrum anti-paramyxoviral activity in vitro and in vivo.
Paramyxoviruses such as human parainfluenza virus type-3 (HPIV3) and measles virus (MeV) are a substantial health threat. In a high-throughput screen for inhibitors of HPIV3 (a major cause of acute respiratory infection), we identified GHP-88309-a non-nucleoside inhibitor of viral polymerase
