2. Academic Validation
  3. A Novel Potent and Highly Specific Inhibitor against Influenza Viral N1-N9 Neuraminidases: Insight into Neuraminidase-Inhibitor Interactions

A Novel Potent and Highly Specific Inhibitor against Influenza Viral N1-N9 Neuraminidases: Insight into Neuraminidase-Inhibitor Interactions

  • J Med Chem. 2016 May 26;59(10):4563-77. doi: 10.1021/acs.jmedchem.5b01863.
Nongluk Sriwilaijaroen 1 2,  Sadagopan Magesh,  Akihiro Imamura,  Hiromune Ando 3,  Hideharu Ishida,  Miho Sakai,  Erika Ishitsubo,  Takanori Hori,  Setsuko Moriya 4,  Takeshi Ishikawa,  Kazuo Kuwata,  Takato Odagiri 5,  Masato Tashiro 5,  Hiroaki Hiramatsu 2,  Kenji Tsukamoto 6,  Taeko Miyagi 4,  Hiroaki Tokiwa,  Makoto Kiso 3,  Yasuo Suzuki 2
Affiliations

Affiliations

  • 1 Department of Preclinical Sciences, Faculty of Medicine, Thammasat University , Pathumthani 12120, Thailand.
  • 2 Health Science Hills, College of Life and Health Sciences, Chubu University , Aichi 487-8501, Japan.
  • 3 Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University , Kyoto 606-8501, Japan.
  • 4 Division of Cancer Glycosylation Research, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University , Sendai 981-8558, Japan.
  • 5 Influenza Virus Research Center, National Institute of Infectious Diseases , Tokyo 208-0011, Japan.
  • 6 Research Team for Zoonotic Diseases, National Institute of Animal Health , Ibaraki 305-0856, Japan.
PMID: 27095056 DOI: 10.1021/acs.jmedchem.5b01863
Abstract

People throughout the world continue to be at risk for death from influenza A virus, which is always creating a new variant. Here we present a new effective and specific anti-influenza viral neuraminidase (viNA) inhibitor, 9-cyclopropylcarbonylamino-4-guanidino-Neu5Ac2en (cPro-GUN). Like zanamivir, it is highly effective against N1-N9 avian and N1-N2 human viNAs, including H274Y oseltamivir-resistant N1 viNA, due to its C-6 portion still being anchored in the active site, different from the disruption of oseltamivir's C-6 anchoring by H274Y mutation. Unlike zanamivir, no sialidase inhibitory activity has been observed for cPro-GUN against huNeu1-huNeu4 Enzymes. Broad efficacy of cPro-GUN against avian and human influenza viruses in cell cultures comparable to its sialidase inhibitory activities makes cPro-GUN ideal for further development for safe therapeutic or prophylactic use against both seasonal and pandemic influenza.

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