Hospices civils de Lyon, Centre de biologie et pathologie Est, Laboratoire de virologie, Lyon, Université de Lyon, Université Lyon 1, CNRS, FRE3011, Laboratoire de virologie et pathogenèse humaine, rue Guillaume-Paradin, 69372 Lyon Cedex 08, Université de Lyon, Université Lyon 1, CNRS, UMR5534, Centre de génétique moléculaire et cellulaire, 16 rue Dubois, 69622 Villeurbanne
Although infections are often subclinical, herpes simplex virus (HSV) can cause mild to severe diseases, especially in immunocompromised patients. There are few drugs licensed for the treatment of HSV infections. Most target the viral DNA polymerase, such as acyclovir that remains the reference treatment some thirty years after its discovery! Extensive clinical use of this drug has led to the emergence of resistant strains, mainly in immunocompromised patients, these infections can be managed with only two drugs, foscarnet and cidofovir, both much more toxic than acyclovir. This highlights the crucial need for the development of new anti-herpes drugs that can inhibit infection by both wild-type viruses and drug-resistant strains. Over the last few years, significant efforts have been made to set up a range of strategies for the identification of potential new antiviral drugs. One alternative is to develop drugs with different mechanisms of action. The present article reviews potential viral and cellular targets that are now known to be involved in HSV multiplication and for which specific inhibitors with anti-HSV activity, at least in cell culture, have been identified. These drugs inhibit viral proteins involved in viral replication (DNA polymerase, ribonucleotide reductase or helicase-primase complex). Other drugs acting on cellular proteins needed for viral replication have also been described; these drugs are targetting cyclin-dependent kinases or the polyamine biosynthetic pathway.