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J Med Chem. 2016 Apr 20. [Epub ahead of print]
A Novel Potent and Highly Specific Inhibitor against Influenza Viral N1-N9 Neuraminidases: Insight into Neuraminidase-inhibitor Interactions.
Sriwilaijaroen N, Sadagopan M, Imamura A, Ando H, Ishida H, Sakai M, Ishitsubo E, Hori T, Moriya S, Ishikawa T, Kuwata K, Odagiri T, Tashiro M, Hiramatsu H, Tsukamoto K, Miyagi T, Tokiwa H, Kiso M, Suzuki Y.
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-cyclopropanecarbonylamino-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.
PMID: 27095056 [PubMed - as supplied by publisher]
A Novel Potent and Highly Specific Inhibitor against Influenza Viral N1-N9 Neuraminidases: Insight into Neuraminidase-inhibitor Interactions.
Sriwilaijaroen N, Sadagopan M, Imamura A, Ando H, Ishida H, Sakai M, Ishitsubo E, Hori T, Moriya S, Ishikawa T, Kuwata K, Odagiri T, Tashiro M, Hiramatsu H, Tsukamoto K, Miyagi T, Tokiwa H, Kiso M, Suzuki Y.
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-cyclopropanecarbonylamino-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.
PMID: 27095056 [PubMed - as supplied by publisher]