Presatovir (GS-5806) (Synonyms: GS-5806)

Presatovir (GS-5806) is a novel, orally bioavailable RSV fusion inhibitor with a mean EC50 value of 0.43 nM.

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[1]. GS-5806 inhibits pre to post triggered conformational changes of RSV F protein, suggesting a possible mechanism for antiviral activity[2].

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[1].

[1]. Mackman RL, et al. Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study. J Med Chem. 2015 Feb 26;58(4):1630-1643. [2]. Samuel D, et al. GS-5806 inhibits pre- to postfusion conformational changes of the respiratory syncytial virus fusion protein. Antimicrob Agents Chemother. 2015 Nov;59(11):7109-12.