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Structure paper

TitleA pan-influenza antibody inhibiting neuraminidase via receptor mimicry.
Journal, issue, pagesNature, Vol. 618, Issue 7965, Page 590-597, Year 2023
Publish dateMay 31, 2023
AuthorsCorey Momont / Ha V Dang / Fabrizia Zatta / Kevin Hauser / Caihong Wang / Julia di Iulio / Andrea Minola / Nadine Czudnochowski / Anna De Marco / Kaitlin Branch / David Donermeyer / Siddhant Vyas / Alex Chen / Elena Ferri / Barbara Guarino / Abigail E Powell / Roberto Spreafico / Samantha S Yim / Dale R Balce / Istvan Bartha / Marcel Meury / Tristan I Croll / David M Belnap / Michael A Schmid / William Timothy Schaiff / Jessica L Miller / Elisabetta Cameroni / Amalio Telenti / Herbert W Virgin / Laura E Rosen / Lisa A Purcell / Antonio Lanzavecchia / Gyorgy Snell / Davide Corti / Matteo Samuele Pizzuto /
PubMed AbstractRapidly evolving influenza A viruses (IAVs) and influenza B viruses (IBVs) are major causes of recurrent lower respiratory tract infections. Current influenza vaccines elicit antibodies ...Rapidly 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 and suboptimal immune responses. 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.
External linksNature / PubMed:37258672 / PubMed Central
MethodsEM (single particle)
Resolution2.2 - 3.1 Å
Structure data

29686

8g30

EMDB-29686, PDB-8g30:
N2 neuraminidase of A/Tanzania/205/2010 H3N2 in complex with 4 FNI19 Fab molecules
Method: EM (single particle) / Resolution: 3.1 Å

29704

8g3m

EMDB-29704, PDB-8g3m:
N2 neuraminidase of A/Tanzania/205/2010 H3N2 in complex with 3 FNI9 Fab molecules
Method: EM (single particle) / Resolution: 3.0 Å

29705

8g3n

EMDB-29705, PDB-8g3n:
N2 neuraminidase of A/Tanzania/205/2010 H3N2 in complex with 4 FNI9 Fab molecules
Method: EM (single particle) / Resolution: 2.9 Å

29706

8g3o

EMDB-29706, PDB-8g3o:
N2 neuraminidase of A/Hong_Kong/2671/2019 in complex with 3 FNI9 Fab molecules
Method: EM (single particle) / Resolution: 3.1 Å

29707

8g3p

EMDB-29707, PDB-8g3p:
N2 neuraminidase of A/Hong_Kong/2671/2019 in complex with 4 FNI9 Fab molecules
Method: EM (single particle) / Resolution: 2.5 Å

29708

8g3q

EMDB-29708, PDB-8g3q:
N2 neuraminidase of A/Tanzania/205/2010 H3N2 in complex with 3 FNI17 Fab molecules
Method: EM (single particle) / Resolution: 2.3 Å

29709

8g3r

EMDB-29709, PDB-8g3r:
N2 neuraminidase of A/Tanzania/205/2010 H3N2 with S245N S247T mutations in complex with one FNI17 Fab molecule
Method: EM (single particle) / Resolution: 2.3 Å

29710

8g3v

EMDB-29710, PDB-8g3v:
N2 neuraminidase of A/Hong_Kong/2671/2019 in complex with 4 FNI19 Fab molecules
Method: EM (single particle) / Resolution: 2.2 Å

29711

8g3z

EMDB-29711, PDB-8g3z:
Neuraminidase of B/Massachusetts/02/2012 (Yamagata) in complex with 4 FNI17 Fab molecules
Method: EM (single particle) / Resolution: 2.3 Å

29712

8g40

EMDB-29712, PDB-8g40:
N2 neuraminidase of A/Hong_Kong/2671/2019 in complex with 3 FNI19 Fab molecules
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • influenza a virus
  • homo sapiens (human)
  • influenza b virus
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / viral glycoprotein / antibody / Fab / influenza / virus / VIRAL PROTEIN-IMMUNE SYSTEM complex

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