Antiviral Effect of Retro-2.1 against Herpes Simplex Virus Type 2 In Vitro

作者：Dai, Wenwen; Wu, Yu; Bi, Jinpeng; Wang, Jingyu; Wang, Shuai; Kong, Wei; Barbier, Julien; Cintrat, Jean-Christophe; Gao, Feng; Jiang, Zhengran; Gillet, Daniel^*; Su, Weiheng^*; Jiang, Chunlai^*

来源：Journal of Microbiology and Biotechnology, 2018, 28(6): 849-859.

DOI：10.4014/jmb.1712.12052

• Herpes simplex virus type 2
• Retro-2.1
• antiviral effect
• entry
• late stage
• vesicle transport

Herpes simplex virus type 2 (HSV-2) infection has been a public health concern worldwide. It is the leading cause of genital herpes and a contributing factor to cervical cancer and human immunodeficiency virus (HIV) infection. No vaccine is available yet for the treatment of HSV2 infection, and routinely used synthetic nucleoside analogs have led to the emergence of drug resistance. The small molecule Retro-2(cycl) has been reported to be active against several pathogens by acting on intracellular vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that Retro-2.1, which is an optimized, more potent derivative of Retro-2(cycl), could inhibit HSV-2 infection, with 50% inhibitory concentrations of 5.58 mu M and 6.35 mu M in cytopathic effect inhibition and plaque reduction assays, respectively. The cytotoxicity of Retro-2.1 was relatively low, with a 50% cytotoxicity concentration of 116.5 mu M. We also preliminarily identified that Retro-2.1 exerted the antiviral effect against HSV-2 by a dual mechanism of action on virus entry and late stages of infection. Therefore, our study for the first time demonstrated Retro-2.1 as an effective antiviral agent against HSV-2 in vitro with targets distinct from those of nucleoside analogs.

• 出版日期2018-6
• 单位中国地震局; 吉林大学