Acyclovir,
valacyclovir, and
famciclovir are used for the treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV)
infections. Helicase-
primase inhibitors (HPIs) inhibit replication fork progression that separates double
DNA strands into two single strands during
DNA synthesis. The HPIs
amenamevir and
pritelivir have novel mechanisms of anti-herpetic action, and their once-daily administration has clinical efficacy for
genital herpes. Among HPIs,
amenamevir has anti-VZV activity. The concentrations of HSV-1 and VZV required for the 50% plaque reduction of
amenamevir were 0.036 and 0.047 μM, respectively. We characterized the features of
amenamevir regarding its mechanism, resistance, and synergism with
acyclovir. Its
antiviral activity was not influenced by the viral replication cycle, in contrast to
acyclovir. A clinical trial of
amenamevir for
herpes zoster demonstrated its non-inferiority to
valacyclovir. To date,
amenamevir has been successfully used in over 1,240,000 patients with
herpes zoster in Japan. Post-marketing surveillance of
amenamevir in Japan reported side effects with significant potential risk identified by the Japanese Risk Management Plan, including
thrombocytopenia, gingival
bleeding, and palpitations, although none of these were serious. The clinical efficacy and safety profiles of
amenamevir were established in patients with
herpes zoster. Therefore,
amenamevir as an HPI opens a new era of anti-herpes
therapy.