Abstract: The present invention provides nucleoside derivatives 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 derivatives 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 derivatives of the present invention.

Abstract: Native Herpes Simplex Virus type 1 (HSV type 1) protease has a rather low activity. It has been found however, that the presence of a kosmotropic anion can increase the activity of the protease over 10-fold. This has many advantages, as now assays for protease activity may be run in very small (micromolar and less) amounts of reagents and substrates, and the assays can be run quickly. Activate HSV-1 protease represents a conformational change from native protease.

Abstract: A method of purifying proteases from the Herpes Simplex Virus 1 and 2 is taught. A precursor protease is cloned in a host cell and then separated from the cell culture using cation exchange chromatography. The resulting protease is subjected to autoprocessing conditions and an autolytic cleavage occurs, resulting in mature protease.