A Novel Potent and Highly Specific Inhibitor against Influenza Viral N1–N9 Neuraminidases: Insight into Neuraminidase–Inhibitor Interactions
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- 作者：Nongluk Sriwilaijaroen ; Sadagopan Magesh ; Akihiro Imamura ; Hiromune Ando ; Hideharu Ishida ; Miho Sakai ; Erika Ishitsubo ; Takanori Hori ; Setsuko Moriya ; Takeshi Ishikawa ; Kazuo Kuwata ; Takato Odagiri ; Masato Tashiro ; Hiroaki Hiramatsu ; Kenji Tsukamoto ; Taeko Miyagi ; Hiroaki Tokiwa ; Makoto Kiso ; Yasuo Suzuki
- 刊名：Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：May 26, 2016
- 年：2016
- 卷：59
- 期：10
- 页码：4563-4577
- 全文大小：969K
- 年卷期：0
- ISSN：1520-4804
文摘
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.