Varicella-zoster virus (VZV), a common and ubiquitous human-restricted pathogen, causes a primary
infection (
varicella or
chickenpox) followed by establishment of latency in sensory ganglia. The virus can reactivate, causing
herpes zoster (HZ,
shingles) and leading to significant morbidity but rarely mortality, although in immunocompromised hosts, VZV can cause severe disseminated and occasionally fatal disease. We discuss VZV diseases and the decrease in their incidence due to the introduction of live-
attenuated vaccines to prevent
varicella or HZ. We also focus on
acyclovir,
valacyclovir, and
famciclovir (FDA approved drugs to treat VZV
infections),
brivudine (used in some European countries) and
amenamevir (a helicase-
primase inhibitor, approved in Japan) that augur the beginning of a new era of anti-VZV
therapy. Valnivudine hydrochloride (FV-100) and
valomaciclovir stearate (in advanced stage of development) and several new molecules potentially good as anti-VZV candidates described during the last year are examined. We reflect on the role of
antiviral agents in the treatment of VZV-associated diseases, as a large percentage of the at-risk population is not immunized, and on the limitations of currently FDA-approved anti-VZV drugs. Their low efficacy in controlling HZ
pain and post-herpetic
neuralgia development, and the need of multiple dosing regimens requiring daily dose adaptation for patients with
renal failure urges the development of novel anti-VZV drugs.