Inhibition of HSV-1 replication and HSV DNA polymerase by the chloroxoquinolinic ribonucleoside 6-chloro-1,4-dihydro-4-oxo-1-(beta-D-ribofuranosyl) quinoline-3-carboxylic acid and its aglycone

Antiviral Res. 2008 Jan;77(1):20-7. doi: 10.1016/j.antiviral.2007.08.011. Epub 2007 Sep 17.


We describe in this paper that the synthetic chloroxoquinolinic ribonucleoside 6-chloro-1,4-dihydro-4-oxo-1-(beta-D-ribofuranosyl) quinoline-3-carboxylic acid (compound A) and its free aglycogene base (compound B) inhibit, with low cytotoxicity, the replication of herpes simplex virus type 1 and 2 (HSV-1 and HSV-2). Compound A inhibited HSV-1 replication in Vero cells with an EC(50) of 1.3 and 1.4 microM for an acyclovir (ACV)-sensitive strain and an ACV-resistant strain of this virus, respectively. Additionally, it inhibited HSV-2 replication with an EC(50) of 1.1 microM. Compound B also inhibited the ACV-sensitive and -resistant HSV-1 strains, and HSV-2 at EC(50) values of 1.7, 1.9 and 1.6 microM, respectively. Time-of-addition assays, performed with compound A, suggested that this molecule at an early time point of the HSV replication cycle. Kinetic assays demonstrated that compounds A and B inhibit the HSV DNA polymerase activity in a noncompetitive fashion, with a K(i) equal to 0.1 and 0.2 microM, respectively. Taken together, our results suggest that compounds A and B represent promising lead molecules for further anti-HSV drug design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / pharmacology*
  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 1, Human / enzymology
  • Herpesvirus 1, Human / physiology
  • Nucleic Acid Synthesis Inhibitors*
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Ribonucleosides / chemistry
  • Ribonucleosides / pharmacology*
  • Vero Cells
  • Virus Replication / drug effects*


  • 6-chloro-1,4-dihydro-4-oxo-1-(beta-D-ribofuranosyl)quinoline-3-carboxylic acid
  • Antiviral Agents
  • Enzyme Inhibitors
  • Nucleic Acid Synthesis Inhibitors
  • Quinolines
  • Ribonucleosides
  • Acyclovir