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Topical application of polyethylenimine as a candidate for novel prophylactic therapeutics against genital herpes caused by herpes simplex virus

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Abstract

Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) cause genital herpes, which can enhance the acquisition of human immunodeficiency virus. The development of anti-HSV agents with novel mechanisms of action is urgently required in the topical therapy of genital herpes. In this study, the in vitro and in vivo anti-HSV effects of Epomin SP-012®, a highly cationic polyethylenimine, were evaluated. When the in vitro antiviral effects of SP-012 were assessed, this compound showed potent activity against HSV-1 and HSV-2. It inhibited the attachment of HSV-2 to host cells and cell-to-cell spread of infection in a concentration-dependent manner and exerted a virucidal effect. No SP-012-resistant HSV-2 was found when the virus was successively passaged in the presence of SP-012. In a mouse genital herpes model, topically administered SP-012 inhibited the progression of the disease caused by HSV infection. These data illustrate that SP-012 may be a novel class of HSV inhibitor that would be acceptable for long-term topical application.

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Acknowledgments

We appreciate Mr. O. Takahashi for high-magnification fluorescence microphotography. This work was supported by a University of Toyama Grant-in-Aid.

Conflict of interest

T.K. is an employee of Nippon Shokubai Co., Ltd., and does not own stock or options in the company. All other authors: nothing to declare.

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Authors and Affiliations

  1. Gradutae School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Kyoko Hayashi, Hiroki Onoue, Kohei Sasaki, Jung-Bum Lee & Toshimitsu Hayashi

  2. Biomedical Research Institute, Central 6, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan

    Penmetcha K. R. Kumar & Subash C. B. Gopinath

  3. Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo, 142-8501, Japan

    Yoshie Maitani

  4. Nippon Shokubai Co. Ltd., Hibiya Dai Bldg. 1-2-2, Uchisaiwai-cho, Chiyoda-ku, Tokyo, 100-0011, Japan

    Takashi Kai

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  1. Kyoko Hayashi
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  2. Hiroki Onoue
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  3. Kohei Sasaki
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  9. Toshimitsu Hayashi
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Correspondence to Kyoko Hayashi.

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Hayashi, K., Onoue, H., Sasaki, K. et al. Topical application of polyethylenimine as a candidate for novel prophylactic therapeutics against genital herpes caused by herpes simplex virus. Arch Virol 159, 425–435 (2014). https://doi.org/10.1007/s00705-013-1829-x

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  • DOI: https://doi.org/10.1007/s00705-013-1829-x

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