Tilorone-Dihydrochloride Protects against Rift Valley Fever Virus Infection and Disease in the Mouse Model.
Tilorone-Dihydrochloride Protects against Rift Valley Fever Virus Infection and Disease in the Mouse Model.
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Tilorone-dhydrocride在小鼠模型中可预防裂谷热病毒感染和疾病。
DOI：
10.3390/microorganisms10010092
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发表时间：
2021-12-31
期刊：
影响因子：
4.5
通讯作者：
Freiberg AN
中科院分区：
文献类型：
--
作者：
Johnson KN;Kalveram B;Smith JK;Zhang L;Juelich T;Atkins C;Ikegami T;Freiberg AN
裂谷热（RVF）是一种蚊媒人畜共患疾病，在非洲和中东地区流行，可影响人类和反刍家畜。目前，尚无经批准的疫苗或治疗剂用于治疗人类严重裂谷热疾病。Tilorone-dihydrochloride（Tilorone）是一种广谱抗病毒候选药物，此前已显示出对多种DNA和RNA病毒的疗效，并在俄罗斯和其他东欧国家临床用于治疗呼吸道感染。在这里，我们评估了替洛龙对裂谷热病毒（RVFV）的抗病毒活性。在体外，替洛龙在低微摩尔浓度下抑制RVFV疫苗株（MP-12）和强毒株（ZH 501）。在小鼠模型中，用替洛龙治疗显著改善了用致死剂量的RVFV ZH 501攻击的BALB/c小鼠的存活结果。感染后立即给药时，30 mg/kg/天剂量组的存活率为80%。在暴露后预防中，当以45 mg/kg/天剂量给药时，感染后1天的替洛龙存活率为30%。这些发现表明，替洛龙在体外和体内对RVFV感染具有有效的抗病毒功效，并支持进一步开发替洛龙作为治疗RVFV感染的潜在抗病毒治疗剂。
Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Middle East that can affect humans and ruminant livestock. Currently, there are no approved vaccines or therapeutics for the treatment of severe RVF disease in humans. Tilorone-dihydrochloride (Tilorone) is a broad-spectrum antiviral candidate that has previously shown efficacy against a wide range of DNA and RNA viruses, and which is clinically utilized for the treatment of respiratory infections in Russia and other Eastern European countries. Here, we evaluated the antiviral activity of Tilorone against Rift Valley fever virus (RVFV). In vitro, Tilorone inhibited both vaccine (MP-12) and virulent (ZH501) strains of RVFV at low micromolar concentrations. In the mouse model, treatment with Tilorone significantly improved survival outcomes in BALB/c mice challenged with a lethal dose of RVFV ZH501. Treatment with 30 mg/kg/day resulted in 80% survival when administered immediately after infection. In post-exposure prophylaxis, Tilorone resulted in 30% survival at one day after infection when administered at 45 mg/kg/day. These findings demonstrate that Tilorone has potent antiviral efficacy against RVFV infection in vitro and in vivo and supports further development of Tilorone as a potential antiviral therapeutic for treatment of RVFV infection.
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