Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Oseltamivir aziridines are potent influenza neuraminidase inhibitors and imaging agents.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 123, Issue 13, Page e2504045123, Year 2026
Publish date	Mar 31, 2026
Authors	Merijn B L Vriends / Elisha Moran / Martín Calvelo / Thomas Hansen / Isabelle B Pickles / Xincheng Xin / Marieke Biezeno / Zachary W B Armstrong / Maria J Ferraz / Lei Li / Alice Lilley / Ruth Harvey / Dmitri V Filippov / Qinghua Liao / Sybrin P Schröder / Gijsbert A van der Marel / Marta Artola / Johannes M F G Aerts / James N Blaza / Jeroen D C Codée / Carme Rovira / Herman S Overkleeft / Gideon J Davies /
PubMed 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 ...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 emerging resistance. We hypothesized that Oseltamivir aziridines would unite transition-state mimicry for tight binding, with aziridine-enabled covalent capture of the catalytic tyrosine, thereby supporting both therapy and activity-based quantification. Here, we present oseltamivir-based aziridines, inspired by cyclophellitol chemistry, that act as covalent inhibitors and activity-based probes via an -acylaziridine warhead. Free-energy calculations, and NMR observations, indicate a H half-chair preference consistent with the NA transition state, and selected analogues inhibit multiple NA subtypes with low nanomolar binding constants. Diverse evidence establishes covalency: time-dependent inactivation, inhibitor washout, intact-mass shifts, MS/MS identification of a tyrosine adduct, and QM/MM reaction profiles, while cryoEM of N1 aligns with the proposed binding mode, revealing an elimination product. The inhibitors demonstrate formidable activity against diverse viral neuraminidases, including H5N1, and further enable imaging and quantification of active NA. With their dual therapeutic and diagnostic potential, these first-in-class inhibitors indeed benefit from transition state mimicry and covalency, and thus offer a powerful platform for antiviral development and neuraminidase imaging, addressing urgent global health needs in influenza treatment and prevention.
External links	Proc Natl Acad Sci U S A / PubMed:41871250
Methods	EM (single particle)
Resolution	2.0 - 2.25 Å
Structure data	52253 9hlg EMDB-52253, PDB-9hlg: Influenza Neuraminidase in complex with N-Acyl Oseltamivir inhibitor Method: EM (single particle) / Resolution: 2.0 Å 52254 9hlh EMDB-52254, PDB-9hlh: Influenza Neuraminidase in complex with N-Acyl Oseltamivir inhibitor Method: EM (single particle) / Resolution: 2.25 Å 52255 9hli EMDB-52255, PDB-9hli: Influenza Neuraminidase in complex with N-Acyl Oseltamivir inhibitor Method: EM (single particle) / Resolution: 2.0 Å
Chemicals	PDB-1ivv: Crystal structure of copper amine oxidase from Arthrobacter globiformis: Early intermediate in topaquinone biogenesis ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-CA: Unknown entry ChemComp-HOH: WATER PDB-1ivw: Crystal structure of copper amine oxidase from Arthrobacter globiformis: Late intermediate in topaquinone biogenesis PDB-1ivx: Crystal structure of copper amine oxidase from Arthrobacter globiformis: Holo form generated by biogenesis in crystal.
Source	influenza a virus
Keywords	VIRAL PROTEIN / Influenza / Neuraminidase