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TitleBroadly neutralizing antibody cocktails targeting Nipah virus and Hendra virus fusion glycoproteins.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 5, Page 426-434, Year 2021
Publish dateApr 29, 2021
AuthorsHa V Dang / Robert W Cross / Viktoriya Borisevich / Zachary A Bornholdt / Brandyn R West / Yee-Peng Chan / Chad E Mire / Sofia Cheliout Da Silva / Antony S Dimitrov / Lianying Yan / Moushimi Amaya / Chanakha K Navaratnarajah / Larry Zeitlin / Thomas W Geisbert / Christopher C Broder / David Veesler /
PubMed AbstractHendra virus (HeV) and Nipah virus (NiV) are henipaviruses (HNVs) causing respiratory illness and severe encephalitis in humans, with fatality rates of 50-100%. There are no licensed therapeutics or ...Hendra virus (HeV) and Nipah virus (NiV) are henipaviruses (HNVs) causing respiratory illness and severe encephalitis in humans, with fatality rates of 50-100%. There are no licensed therapeutics or vaccines to protect humans. HeV and NiV use a receptor-binding glycoprotein (G) and a fusion glycoprotein (F) to enter host cells. HNV F and G are the main targets of the humoral immune response, and the presence of neutralizing antibodies is a correlate of protection against NiV and HeV in experimentally infected animals. We describe here two cross-reactive F-specific antibodies, 1F5 and 12B2, that neutralize NiV and HeV through inhibition of membrane fusion. Cryo-electron microscopy structures reveal that 1F5 and 12B2 recognize distinct prefusion-specific, conserved quaternary epitopes and lock F in its prefusion conformation. We provide proof-of-concept for using antibody cocktails for neutralizing NiV and HeV and define a roadmap for developing effective countermeasures against these highly pathogenic viruses.
External linksNat Struct Mol Biol / PubMed:33927387
MethodsEM (single particle)
Resolution2.8 - 2.9 Å
Structure data

22884

7ki4

EMDB-22884, PDB-7ki4:
Structure of the NiV F glycoprotein in complex with the 12B2 neutralizing antibody
Method: EM (single particle) / Resolution: 2.9 Å

22885

7ki6

EMDB-22885, PDB-7ki6:
Structure of the HeV F glycoprotein in complex with the 1F5 neutralizing antibody
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • nipah virus
  • mus musculus (house mouse)
  • hendra henipavirus
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Nipah virus / Hendra virus / henipavirus / neutralizing antibody / monoclonal antibody / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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