691852-58-1

EC50: 9 nM (NS3 ^V170A ), 13 nM (NS3 ^V170A ), 15 nM (NS3 ^K583T ), 13 nM (NS5B ^I424V )

Replicon cells are treated with 1 mg/mL G418 and combinations of the two compounds. Nesbuvir (HCV-796) is added to 40 or 80 nM (approximately 10 and 20 times the EC ₅₀ in a 3-day replicon inhibition assay, respectively) and Boceprevir is added to 400 or 800 nM (approximately 2 and 4 times the EC ₅₀ , respectively). The EC ₅₀ s for Nesbuvir and Boceprevir for the parental replicon in the transient expression assay are comparable to those obtained in the 3-day inhibition assay with the stable replicon cells; the EC ₅₀ for Nesbuvir in the transient expression assay is 14 nM, whereas it is 5 nM for the stable replicon; and the EC ₅₀ for Boceprevir in the transient expression assay is 608 nM, whereas it is 201 nM for the stable replicon.

Among a huge variety of yet characterized nucleoside and non-nucleoside inhibitors (NNI), the benzofurane derivative NNI Nesbuvir (HCV-796) is demonstrated to yield significant antiviral effects in mice with chimeric human livers and in patients infected with HCV. HCV-796 binds to a hydrophobic binding pocket at the “palm” domain of NS5B; however, its mode of inhibition remains to be defined.