State Key Laboratory of Virology, Institute of Medical Virology, National Laboratory of Antiviral and Tumour of Traditional Chinese Medicine, Hubei Province Key Laboratory of Allergy and Immunology, School of Medicine of Wuhan University, Wuhan 430071, China; Guangzhou Institutes of Biomedicine and Heath, Chinese Academy of Sciences, 190 Kaiyuan Road, Guangzhou 510530, China.
State Key Laboratory of Virology, Institute of Medical Virology, National Laboratory of Antiviral and Tumour of Traditional Chinese Medicine, Hubei Province Key Laboratory of Allergy and Immunology, School of Medicine of Wuhan University, Wuhan 430071, China.
Int J Antimicrob Agents. 2018 Jan;51(1):98-106. doi: 10.1016/j.ijantimicag.2017.09.001. Epub 2017 Sep 7.
Herpes simplex virus type 1 (HSV-1) causes significant human diseases ranging from skin lesions to encephalitis, especially in neonates and immunocompromised hosts. The discovery of novel anti-HSV-1 drugs with low toxicity is required for public health. Arbidol hydrochloride (ARB) is an indole derivative molecule with broad-spectrum antiviral activity. In this study, the antiviral effects of ARB against HSV-1 infection were evaluated in vitro and in vivo. The results showed that ARB presents significant inhibitory effect on HSV-1 plaque formation and generation of progeny virus, with EC50 values (50% effective concentration) of 5.39 µg/mL (10.49 µM) and 2.26 µg/mL (4.40 µM), respectively. Moreover, time-of-addition and time-of-removal assays further suggested that ARB has viral inhibitory effects when added up to 12 h post-infection (p.i.), which could be further corroborated by determining the expression of viral immediate-early (ICP4, ICP22 and ICP27), early (ICP8 and UL42) and late (gB, gD, gH, VP1/2 and VP16) genes by real-time quantitative PCR as well as the expression of viral protein ICP4 and ICP8 at 6 h and 12 h p.i. Results of the in vivo study showed that ARB could reduce guinea pig skin lesions caused by HSV-1 infection. Conclusively, this report offers new perspectives in the search for therapeutic measures in the treatment of HSV-1 infection.
单纯疱疹病毒 1 型 (HSV-1) 可引起从皮肤损伤到脑炎等多种人类重大疾病，尤其是在新生儿和免疫功能低下的宿主中。为了公共卫生健康，需要开发具有低毒性的新型抗 HSV-1 药物。盐酸阿比多尔 (ARB) 是一种具有广谱抗病毒活性的吲哚衍生物分子。在本研究中，评估了 ARB 对 HSV-1 感染的体外和体内抗病毒作用。结果表明，ARB 对 HSV-1 噬斑形成和子代病毒生成具有显著的抑制作用，EC50 值（半数有效浓度）分别为 5.39μg/mL（10.49μM）和 2.26μg/mL（4.40μM）。此外，添加时间和去除时间测定进一步表明，ARB 在感染后 12 小时内添加时具有病毒抑制作用，通过实时定量 PCR 测定病毒即刻早期 (ICP4、ICP22 和 ICP27)、早期 (ICP8 和 UL42) 和晚期 (gB、gD、gH、VP1/2 和 VP16) 基因的表达以及感染后 6 小时和 12 小时 ICP4 和 ICP8 病毒蛋白的表达，可进一步证实这一点。体内研究结果表明，ARB 可减少 HSV-1 感染引起的豚鼠皮肤损伤。总之，本报告为寻找治疗 HSV-1 感染的治疗措施提供了新的视角。
