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Glycoconjugate Journal

, Volume 29, Issue 4, pp 231–237 | Cite as

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

  • Yuji Itoh
  • Ayumi Sando
  • Kiyoshi Ikeda
  • Takashi Suzuki
  • Hiroaki Tokiwa
Article

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.

Keyword

Human parainfluenza Anti-hPIV drug Fragment molecular orbital First-principles calculation Neu5Ac CH-π interaction 

Notes

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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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Yuji Itoh
    • 1
  • Ayumi Sando
    • 1
  • Kiyoshi Ikeda
    • 2
  • Takashi Suzuki
    • 3
  • Hiroaki Tokiwa
    • 1
    • 4
  1. 1.Department of Chemistry, Faculty of ScienceRikkyo UniversityTokyoJapan
  2. 2.Department of Pharmaceutical SciencesHiroshima International UniversityHiroshimaJapan
  3. 3.Department of BiochemistryUniversity of ShizuokaShizuokaJapan
  4. 4.Research Center for Smart MoleculesRikkyo UniversityTokyoJapan

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