National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM120553
United States
Citation
Journal: Nat Struct Mol Biol / Year: 2019 Title: An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections. Authors: Ha V Dang / Yee-Peng Chan / Young-Jun Park / Joost Snijder / Sofia Cheliout Da Silva / Bang Vu / Lianying Yan / Yan-Ru Feng / Barry Rockx / Thomas W Geisbert / Chad E Mire / Christopher C ...Authors: Ha V Dang / Yee-Peng Chan / Young-Jun Park / Joost Snijder / Sofia Cheliout Da Silva / Bang Vu / Lianying Yan / Yan-Ru Feng / Barry Rockx / Thomas W Geisbert / Chad E Mire / Christopher C Broder / David Veesler / Abstract: Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50-100%. No vaccines or licensed ...Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50-100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals.
Resolution: 1.483→68.6 Å / Cor.coef. Fo:Fc: 0.979 / Cor.coef. Fo:Fc free: 0.97 / SU B: 3.593 / SU ML: 0.055 / SU R Cruickshank DPI: 0.0647 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.065 / ESU R Free: 0.06 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
Rfactor
Num. reflection
% reflection
Selection details
Rfree
0.1733
4238
5 %
RANDOM
Rwork
0.1372
-
-
-
obs
0.139
79965
99.61 %
-
Solvent computation
Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
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