Amenamevir, a Helicase-Primase Inhibitor, for the Optimal Treatment of Herpes Zoster.
Amenamevir, a Helicase-Primase Inhibitor, for the Optimal Treatment of Herpes Zoster.
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DOI：
10.3390/v13081547
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发表时间：
2021-08-05
期刊：
影响因子：
--
通讯作者：
Fukuda H
中科院分区：
文献类型：
--
作者：
Shiraki K;Yasumoto S;Toyama N;Fukuda H
阿昔洛韦、伐昔洛韦和泛昔洛韦用于治疗单纯疱疹病毒（HSV）和水痘-带状疱疹病毒（VZV）感染。解旋酶-引发酶抑制剂（HPI）抑制在DNA合成期间将双DNA链分离成两条单链的复制叉进展。HPI amenamevir和pritelivir具有新的抗疱疹作用机制，每日一次给药对生殖器疱疹具有临床疗效。在HPI中，amenamevir具有抗VZV活性。Amenamevir减少50%空斑所需的HSV-1和VZV浓度分别为0.036和0.047 μM。我们的特点，阿米那韦的机制，耐药性，并与阿昔洛韦的协同作用。与阿昔洛韦相反，其抗病毒活性不受病毒复制周期的影响。治疗带状疱疹的一项临床试验证实了阿米那韦的非劣效性。迄今为止，amenamevir已在日本成功用于超过1，240，000名带状疱疹患者。在日本，amenamevir的上市后监测报告了日本风险管理计划确定的具有重大潜在风险的副作用，包括血小板减少症、牙龈出血和心悸，尽管这些都不是严重的。在带状疱疹患者中确立了氨美韦的临床疗效和安全性。因此，amenamevir作为HPI开启了抗疱疹治疗的新时代。
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.
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