Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Isis Pharmaceuticals, Inc.

Amy L Simcoe

Robert L LaFemina

Steven W Ludmerer

Osvaldo A Flores

Donald J Graham

Phillip Dan Cook

Thazha P Prakash

Balkrishen Bhat

Anne Bettina Eldrup

Mario A Valenciano

Carrie A Rutkowski

The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.

Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase

The present invention features NS5B polypeptides from different clinically important HCV genotypes. The polypeptides can be used individually, or as part of a panel of RNA-dependent RNA polymerases, to evaluate the effectiveness of a compound to inhibit NS5B activity.

HCV RNA-dependent RNA polymerase

Growing community of inventors

Collegeville, PA, United States of America

Amy L Simcoe