8g3n | pdb_00008g3n
N2 neuraminidase of A/Tanzania/205/2010 H3N2 in complex with 4 FNI9 Fab molecules
Structural highlights
FunctionA0A4D6K9W1_9INFA Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft-association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication.[HAMAP-Rule:MF_04071] Publication Abstract from PubMedRapidly evolving influenza A viruses (IAVs) and influenza B viruses (IBVs) are major causes of recurrent lower respiratory tract infections. Current influenza vaccines elicit antibodies predominantly to the highly variable head region of haemagglutinin and their effectiveness is limited by viral drift(1) and suboptimal immune responses(2). Here we describe a neuraminidase-targeting monoclonal antibody, FNI9, that potently inhibits the enzymatic activity of all group 1 and group 2 IAVs, as well as Victoria/2/87-like, Yamagata/16/88-like and ancestral IBVs. FNI9 broadly neutralizes seasonal IAVs and IBVs, including the immune-evading H3N2 strains bearing an N-glycan at position 245, and shows synergistic activity when combined with anti-haemagglutinin stem-directed antibodies. Structural analysis reveals that D107 in the FNI9 heavy chain complementarity-determinant region 3 mimics the interaction of the sialic acid carboxyl group with the three highly conserved arginine residues (R118, R292 and R371) of the neuraminidase catalytic site. FNI9 demonstrates potent prophylactic activity against lethal IAV and IBV infections in mice. The unprecedented breadth and potency of the FNI9 monoclonal antibody supports its development for the prevention of influenza illness by seasonal and pandemic viruses. A pan-influenza antibody inhibiting neuraminidase via receptor mimicry.,Momont C, Dang HV, Zatta F, Hauser K, Wang C, di Iulio J, Minola A, Czudnochowski N, De Marco A, Branch K, Donermeyer D, Vyas S, Chen A, Ferri E, Guarino B, Powell AE, Spreafico R, Yim SS, Balce DR, Bartha I, Meury M, Croll TI, Belnap DM, Schmid MA, Schaiff WT, Miller JL, Cameroni E, Telenti A, Virgin HW, Rosen LE, Purcell LA, Lanzavecchia A, Snell G, Corti D, Pizzuto MS Nature. 2023 Jun;618(7965):590-597. doi: 10.1038/s41586-023-06136-y. Epub 2023 , May 31. PMID:37258672[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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