Presatovir

Presatovir (GS-5806) is a novel, orally bioavailable RSV fusion inhibitor (mean EC50: 0.43 nM) .Presatovir exhibits potent activity against a wide range of RSV A and B clinical isolates (mean EC50: 0.43 nM) . GS-5806 inhibits pre to post triggered conformational changes of RSV F protein, suggesting a possible mechanism for antiviral activity.In a cotton rat model of RSV infection, Presatovir demonstrates dose-dependent (0-30 mg/kg) antiviral efficacy. Oral bioavailability in preclinical species ranges from 46 to 100%, with penetration of the compound into the lung tissue demonstrated in Sprague-Dawley rats. Multidose oral treatment of Presatovir appears safe in adults, and in healthy human volunteers experimentally infected with RSV, a potent antiviral effect and reduction in disease severity are observed in the high dose group. (In Vitro) :Presatovir is a novel, orally bioavailable RSV fusion inhibitor discovered following a lead optimization campaign on a hit originated from a phenotypic RSV antiviral high-throughput screen. Presatovir exhibits potent activity against a wide range of RSV A and B clinical isolates with a mean EC50 value of 0.43 nM. GS-5806 inhibits pre to post triggered conformational changes of RSV F protein, suggesting a possible mechanism for antiviral activity. (In Vivo) :Presatovir demonstrates dose-dependent (0-30 mg/kg) antiviral efficacy in a cotton rat model of RSV infection. Oral bioavailability in preclinical species ranges from 46 to 100%, with penetration of the compound into the lung tissue demonstrated in Sprague-Dawley rats. Multidose oral treatment of Presatovir appears safe in adults, and in healthy human volunteers experimentally infected with RSV, a potent antiviral effect and reduction in disease severity is observed in the high dose group. A group treated with a lower dose of Presatovir allows for a PK-PD relationship to be established to help guide future dose selections.