SR-2P vaginal microbicide gel provides protection against herpes simplex virus 2 when administered as a combined prophylactic and postexposure therapeutic.
SR-2P vaginal microbicide gel provides protection against herpes simplex virus 2 when administered as a combined prophylactic and postexposure therapeutic.
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SR-2P 阴道杀菌剂凝胶作为预防性药物和暴露后治疗药物联合使用时，可提供针对单纯疱疹病毒 2 型的保护。
DOI：
10.1128/aac.00690-15
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发表时间：
2015
影响因子：
4.9
通讯作者：
Shankar,GitaN
中科院分区：
文献类型：
--
作者：
Fields,ScottA;Bhatia,Gaurav;Fong,JulieM;Liu,Mingtao;Shankar,GitaN
以前，我们证明了单一预防剂量的SR-2 P，一种新型的双组分杀微生物剂凝胶，包括阿昔洛韦和替诺福韦，导致小鼠存活率适度增加后，单纯疱疹病毒2（HSV-2）的致命挑战。在这里，我们表明，在感染前24小时给予SR-2 P的剂量提供了一些针对病毒的保护，但程度低于SR-2 P每天一次，持续2天或感染前1小时。所有预防性剂量均不能阻断病毒感染，所有剂量均导致80 - 100%的致死率。然而，考虑到预防性剂量仍然显著降低了总体临床评分，降低了体重减轻率，并增加了小鼠的中位生存期，我们研究了除了预防性剂量外，重复给药方案（感染后）是否可以预防死亡并降低小鼠中的病毒水平。几乎所有（每组10只中的9只）在感染前接受SR-2 P 2天或在感染前1小时接受SR-2 P并在感染后10天每天一次给予SR-2 P的小鼠均未显示感染的临床症状，阴道拭子中无病毒载量，并在感染后存活28天。相反，未接受治疗或接受相同媒介物治疗的小鼠表现出晚期临床体征，并且在感染后第9天不能存活。我们认为SR-2 P是一种有效的抗HSV-2的药物。
Previously, we demonstrated that a single prophylactic dose of SR-2P, a novel dual-component microbicide gel comprising acyclovir and tenofovir, led to a modest increase in mouse survival following a lethal challenge of herpes simplex virus 2 (HSV-2). Here, we show that a dose of SR-2P administered 24 h prior to infection provides some protection against the virus, but to a lesser degree than SR-2P administered either once a day for 2 days or 1 h prior to infection. None of the prophylactic doses blocked infection by the virus, and all resulted in 80 to 100% lethality. However, given that a prophylactic dose still provided a significant reduction in overall clinical score, reduced rate of body weight loss, and increased median survival of the mice, we examined whether a repetitive dose regimen (postinfection) in addition to the prophylactic dose could prevent death and reduce the levels of virus in mice. Nearly all (9 of 10 in each group) of the mice that received SR-2P for 2 days prior to infection or that received SR-2P 1 h prior to infection and were administered SR-2P once a day for 10 days after infection showed no clinical symptoms of infection and no viral loads in vaginal swabs and survived for 28 days postinfection. Conversely, mice receiving no treatment or an identical vehicle treatment demonstrated advanced clinical signs and did not survive past day 9 postinfection. We conclude that SR-2P is an effective anti-HSV-2 agent in mice.