HCV NS5B polymerase-bound conformation of a soluble sulfonamide inhibitor by 2D tranferred NOESY

HCV NS5B RNA-dependent RNA polymerase (NS5B) is essential for viral replication and is therefore considered a target for antiviral drug development. From our ongoing screening e\ufb00ort in the search for new anti-HCV agents, a novel inhibitor 1 with low lM activity against the HCV NS5B polymerase was identi\ufb01ed. SAR analysis indicated the optimal substitution pattern required for activity, for example, carboxylic acid group at 2-position of thiophene ring. We describe the steps taken to identify and solve the bioactive conformation of derivative 6 through the use of the transferred NOE method (trNOE).NRC publication: Ye