5jyy

Structure-based Tetravalent Zanamivir with Potent Inhibitory Activity against Drug-resistant Influenza Viruses

spinqualitylabelsall models 5jyy, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5jyy is a 1 chain structure with sequence from 9infa. This structure supersedes the now removed PDB entry 5e6l. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 6PY, BMA, CA, MAN, NAG Related: 4mwx Gene: NA (9INFA) Activity: Exo-alpha-sialidase, with EC number 3.2.1.18 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [R4NFR6_9INFA] Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates.[RuleBase:RU361252] Publication Abstract from PubMed Zanamivir and oseltamivir are principal influenza antiviral drugs that target viral neuraminidase (NA), but resistant viruses containing mutant NAs with diminished drug affinity are increasingly emerging. Using the structural knowledge of both drug-binding sites and their spatial arrangement on the homotetrameric NA, we have developed a tetravalent zanamivir (TZ) molecule that exhibited marked increases in NA binding affinity, inhibition of NA enzyme activity, and in vitro plus in vivo antiviral efficacy over zanamivir. TZ functioned against both human seasonal H3N2 and avian H7N9 viruses, including drug-resistant mutants. Crystal structure of a resistant N9 NA in complex with TZ explained the function, which showed that four zanamivir residues simultaneously bound to all four monomers of NA. The design method of TZ described in this study may be useful to develop drugs or ligands that target proteins with multiple binding sites. The potent anti-influenza activity of TZ makes it attractive for further development. Structure-Based Tetravalent Zanamivir with Potent Inhibitory Activity against Drug-Resistant Influenza Viruses.,Fu L, Bi Y, Wu Y, Zhang S, Qi J, Li Y, Lu X, Zhang Z, Lv X, Yan J, Gao GF, Li X J Med Chem. 2016 Jul 6. PMID:27341624 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Neuraminidase

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