Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Antiviral Effect of Retro-2.1 against Herpes Simplex Virus Type 2 In Vitro

  • Dai, Wenwen (National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University) ;
  • Wu, Yu (Joliot, CEA, LabEx LERMIT, Universite Paris-Saclay) ;
  • Bi, Jinpeng (National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University) ;
  • Wang, Jingyu (National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University) ;
  • Wang, Shuai (National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University) ;
  • Kong, Wei (National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University) ;
  • Barbier, Julien (Joliot, CEA, LabEx LERMIT, Universite Paris-Saclay) ;
  • Cintrat, Jean-Christophe (Joliot, CEA, LabEx LERMIT, Universite Paris-Saclay) ;
  • Gao, Feng (National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University) ;
  • Jiang, Zhengran (Maclay School) ;
  • Gillet, Daniel (Joliot, CEA, LabEx LERMIT, Universite Paris-Saclay) ;
  • Su, Weiheng (National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University) ;
  • Jiang, Chunlai (National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University)
  • Received : 2017.12.27
  • Accepted : 2018.04.09
  • Published : 2018.06.28
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Abstract

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 HSV-2 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.

Keywords

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