ETIDIOH - NEW

  Highlights •  A detailed phylogenetic analysis of H5N1 HPAIV isolated from humans was performed. •  All strains infecting humans have acquired substitutions in several key proteins. •  All strains have gained specific substitutions to better adapt to the human host. •  Substitutions in key proteins involved in replication and immune evasion were found. •  A significant degree of polymorphic sites was found in the polymerase complex. •  Substitutions in hemagglutinins and neuraminidases from different clades were found. Abstract Avian Influenza Viruses (AIVs) pose today a very significant risk to global health given the widespread circulation of H5N1 highly pathogenic avian influenza viruses (HPAIV). After decimating the avian population all over the world, these viruses spill over to many different mammal species , causing also fatal outbreaks. As the virus continues to evolve increasing human cases of H5N1 HPAIV have been reported, causing concern t...

  Significance Influenza remains a major global health threat . We introduce oseltamivir-based aziridines that unite transition-state mimicry for tight binding with aziridine-enabled covalent capture of the catalytic tyrosine . This dual function yields potent, mechanism-based neuraminidase inhibition and enables activity-based quantification of active enzyme directly in complex samples. Across N1, N2, and influenza B enzymes , selected compounds show high potency against diverse viral neuraminidases and in live virus replication assays. By combining a clinically grounded scaffold with a reactivity handle, these molecules bridge therapeutic and diagnostic needs and offer a practical platform for neuraminidase imaging and antiviral development. Abstract Influenza neuraminidase (NA) is a critical target for seasonal and pandemic antivirals , including the strains of current concern. Current treatments, such as Zanamivir and Oseltamivir , are limited by noncovalent binding and emergin...