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-Structure paper
タイトル | Broadly neutralizing antibody cocktails targeting Nipah virus and Hendra virus fusion glycoproteins. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 28, Issue 5, Page 426-434, Year 2021 |
掲載日 | 2021年4月29日 |
![]() | Ha 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 要旨 | 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 ...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. |
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手法 | EM (単粒子) |
解像度 | 2.8 - 2.9 Å |
構造データ | EMDB-22884, PDB-7ki4: EMDB-22885, PDB-7ki6: |
化合物 | ![]() ChemComp-NAG: |
由来 |
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![]() | VIRAL 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 |