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

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.