Evaluation of Lassa antiviral compound ST-193 in a guinea pig model.
Evaluation of Lassa antiviral compound ST-193 in a guinea pig model.
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DOI：
10.1016/j.antiviral.2011.02.012
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发表时间：
2011-04
影响因子：
7.6
通讯作者：
Guttieri, Mary C.
中科院分区：
文献类型：
--
作者：
Cashman, Kathleen A.;Smith, Mark A.;Twenhafel, Nancy A.;Larson, Ryan A.;Jones, Kevin F.;Allen, Robert D., III;Dai, Dongcheng;Chinsangaram, Jarasvech;Bolken, Tove' C.;Hruby, Dennis E.;Amberg, Sean M.;Hensley, Lisa E.;Guttieri, Mary C.
拉萨病毒(LASV)是Arenaviridae家族的成员，它引起一种流行于西非的病毒性出血热，那里每年有多达30万人感染。目前，还没有FDA批准的LASV特异性疫苗或抗病毒药物，尽管抗病毒药物利巴韦林已经显示出一些效果。新近发现的ArenaVirus进入的小分子抑制剂ST-193在体外表现出亚微摩尔的抗病毒活性。为了确定ST-193在体内的抗病毒作用，我们在LASV豚鼠模型上测试了该化合物的疗效。13号品系豚鼠分4组，分别给予25或80 mg/kg的ST-193、25 mg/kg的利巴韦林或赋形剂(Ip)。在感染致死剂量的LASV菌株Josiah之前，每天持续一次，持续14天。对照动物表现出严重的疾病，在感染后10至15天内死亡。与利巴韦林组或赋形剂组相比，ST-193处理的动物表现出较少的疾病迹象并提高了存活率。在感染ST-193的大多数动物中，所有组的体温在感染后第9天升高，但在第19天恢复正常。与赋形剂治疗的对照组相比，ST-193治疗使病毒血症减少了2-3个对数。经ST-193处理的豚鼠的总存活率为62.5%(10/16)，而利巴韦林组(0/8)和赋形剂组(0/7)的存活率为0。这些数据表明，ST-193可能是治疗拉沙热的改进候选药物。
Lassa virus (LASV), a member of the Arenaviridae family, causes a viral hemorrhagic fever endemic to West Africa, where as many as 300,000 infections occur per year. Presently, there are no FDA-approved LASV-specific vaccines or antiviral agents, although the antiviral drug ribavirin has shown some efficacy. A recently identified small-molecule inhibitor of arenavirus entry, ST-193, exhibits submicromolar antiviral activity in vitro. To determine the antiviral utility of ST-193 in vivo, we tested the efficacy of this compound in the LASV guinea pig model. Four groups of strain 13 guinea pigs were administered 25 or 80 mg/kg ST-193, 25 mg/kg of ribavirin, or the vehicle by the intraperitoneal (i.p.) route before infection with a lethal dose of LASV, strain Josiah, and continuing once daily for 14 days. Control animals exhibited severe disease, becoming moribund between days 10 and 15 postinfection. ST-193-treated animals exhibited fewer signs of disease and enhanced survival when compared to the ribavirin or vehicle groups. Body temperatures in all groups were elevated by day 9, but returned to normal by day 19 postinfection in the majority of ST-193-treated animals. ST-193 treatment mediated a 2–3-log reduction in viremia relative to vehicle-treated controls. The overall survival rate for the ST-193-treated guinea pigs was 62.5% (10/16) compared with 0% in the ribavirin (0/8) and vehicle (0/7) groups. These data suggest that ST-193 may serve as an improved candidate for the treatment of Lassa fever.
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DOI：
10.4269/ajtmh.1970.19.670
发表时间：
1970-01-01
影响因子：
3.3
作者：
FRAME, JD;BALDWIN, JM;TROUP, JM
通讯作者：
TROUP, JM
影响因子：
--
作者：
FISHERHOCH, SP;TOMORI, O;MCCORMICK, JB
通讯作者：
MCCORMICK, JB
影响因子：
5.4
作者：
Eschli, Bruno;Quirin, Katharina;Hengartner, Hans
通讯作者：
Hengartner, Hans
影响因子：
1.8
作者：
Drapeau, C. M. J.;Remotti, D.;Petrosillo, N.
通讯作者：
Petrosillo, N.
影响因子：
15.8
作者：
Geisbert TW;Jones S;Fritz EA;Shurtleff AC;Geisbert JB;Liebscher R;Grolla A;Ströher U;Fernando L;Daddario KM;Guttieri MC;Mothé BR;Larsen T;Hensley LE;Jahrling PB;Feldmann H
通讯作者：
Feldmann H