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Origin of the inhibitory activity of 4-O-substituted sialic derivatives of human parainfluenza virus

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Abstract

Human parainfluenza virus (hPIV) is a serious human pathogen causing upper and lower respiratory tract disease, yet there are no effective vaccines or therapies to control parainfluenza virus infections. Recently, we found that 4-O-substituted sialic derivatives have potent inhibitory activity against hPIV-1, whereas the anti-influenza inhibitor Zanamivir was less inhibitory. To elucidate the origin of the high potency inhibitory activities of these 4-O-substituted derivatives, we performed correlated fragment molecular orbital (FMO)-interfragment interaction energy (IFIE) analysis for hemagglutinin-neuraminidase (HN) glycoprotein complexes of hPIV with the derivatives and compared them with those for Zanamivir. We found key interactions between the inhibitors and the hPIV HN glycoprotein and identified important factors for the inhibitory activity. These theoretical results will be useful for the development of novel anti-hPIV drugs.

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Acknowledgments

The study was supported in part by the Grant-in-Aid for Scientific Research <KAKENHI> (C) (grant number 21590128 to H.T.) from the Ministry of Education, Culture, Sports, Science and Technology, (MEXT) Japan. H.T. acknowledges MEXT – Supported Program for the Strategic Research Foundation at Private Universities, 2009-2014.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo, 171-8501, Japan

    Yuji Itoh, Ayumi Sando & Hiroaki Tokiwa

  2. Department of Pharmaceutical Sciences, Hiroshima International University, 5-5-1 Hirokoshingai, Kure, Hiroshima, 737-0112, Japan

    Kiyoshi Ikeda

  3. Department of Biochemistry, University of Shizuoka, Yada 52-1, Suruga-ku, Shizuoka, 422-8526, Japan

    Takashi Suzuki

  4. Research Center for Smart Molecules, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo, 171-8501, Japan

    Hiroaki Tokiwa

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  1. Yuji Itoh
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  2. Ayumi Sando
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  3. Kiyoshi Ikeda
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  4. Takashi Suzuki
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  5. Hiroaki Tokiwa
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Correspondence to Hiroaki Tokiwa.

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Itoh, Y., Sando, A., Ikeda, K. et al. Origin of the inhibitory activity of 4-O-substituted sialic derivatives of human parainfluenza virus. Glycoconj J 29, 231–237 (2012). https://doi.org/10.1007/s10719-012-9384-3

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  • DOI: https://doi.org/10.1007/s10719-012-9384-3

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