PC786

PC786 is an inhaled respiratory syncytial virus (RSV) L protein polymerase inhibitor. PC786 demonstrates potent antiviral activity against RSV-A (IC₅₀ <0.09 to 0.71 nM) and RSV-B (IC₅₀, 1.3 to 50.6 nM)^[1]. In Vitro: PC786 demonstrates a potent and selective antiviral activity against laboratory-adapted or clinical isolates of RSV-A (IC₅₀<0.09 to 0.71 nM) and RSV-B (IC₅₀, 1.3 to 50.6 nM), which are determined by inhibition of cytopathic effects in HEp-2 cells without causing detectable cytotoxicity. PC786 inhibits RSV A2 activity, exhibiting an IC₅₀ and IC₉₀ of 0.50±0.0014 nM and 0.63±0.035 nM, respectively. PC786 inhibits RSV B WST activity, exhibiting an IC₅₀ and IC₉₀ of 27.3±0.77 nM and 57.1±3.87 nM, respectively. PC786 exhibits potent inhibition of cytopathic effect (CPE) induced by known RSV A clinical isolates (IC₅₀, 0.14 to 3.2 nM). PC786 also exhibits potent inhibition of CPE induced by various low-passage-number clinical isolates of RSV A (IC₅₀, 0.42 nM [median]) and RSV B (IC₅₀, 17.5 nM [median])^[1]. In Vivo: Once-daily treatment with PC786, on days-1 to 3, by either intratracheal (i.t.) or intranasal (i.n.) administration, is found to inhibit viral loads in the lungs of RSV A2-infected BALB/c mice. The viral load is below the level of detection when the drug is given at 2 mg/mL (40 μg/mouse [approximately 1.6 mg/kg of body weight] for i.t. treatment, or 80 μg/mouse [approximately 3.2 mg/kg] for i.n. treatment)^[1].