Ledipasvir hydrochloride (GS-5885) is a hepatitis C virus NS5A inhibitor, demonstrating potent activity with EC50 values of 34 pM for genotype 1a replicon and 4 pM for genotype 1b replicon. It also functions as a SARS-CoV 3CL pro inhibitor with an IC50 of 1.62 µM [3].

Ledipasvir hydrochloride exhibits potent antiviral activity with EC50 values of 31 pM for GT1a and 4 pM for GT1b. When protein-adjusted, these values rise to 210 pM for GT1a and 27 pM for GT1b. The compound's intrinsic EC50 for GT1a is 310 fM and for GT1b is 40 fM. It is noted for high protein binding in both human serum and 10% BSA-containing cell-culture media used in replicon assays [1]. Additionally, ledipasvir hydrochloride demonstrates an EC50 value of 141 nM against the JFH/3a-NS5A replicon [2].

Ledipasvir hydrochloride is distinguished by its potent replicon inhibition, complemented by low systemic clearance, favorable bioavailability, and extended half-lives in rat (1.83 hr), dog (2.63 hr), and monkey species, with similarly low clearance projected for humans. Its pharmacokinetics reveal moderate volumes of distribution (Vss) exceeding total body water and consistent half-lives in both rat and dog plasma.