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

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Abstract

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 effort in the search for new anti-HCV agents, a novel inhibitor 1 with low μM activity against the HCV NS5B polymerase was identified. 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).

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Acknowledgements

We thank Thérèse Godbout for her assistance in the preparation of this manuscript.

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