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Structure of the prefusion-locking broadly neutralizing antibody RVC20 bound to the rabies virus glycoprotein

Author

Listed:
  • Jan Hellert

    (Structural Virology Unit, Institut Pasteur)

  • Julian Buchrieser

    (Institut Pasteur)

  • Florence Larrous

    (Institut Pasteur)

  • Andrea Minola

    (Humabs BioMed SA, a subsidiary of Vir Biotechnology Inc.)

  • Guilherme Dias Melo

    (Institut Pasteur)

  • Leah Soriaga

    (Vir Biotechnology Inc)

  • Patrick England

    (Molecular Biophysics Platform C2RT, Institut Pasteur)

  • Ahmed Haouz

    (Crystallography Platform C2RT, Institut Pasteur)

  • Amalio Telenti

    (Vir Biotechnology Inc)

  • Olivier Schwartz

    (Institut Pasteur)

  • Davide Corti

    (Humabs BioMed SA, a subsidiary of Vir Biotechnology Inc.)

  • Hervé Bourhy

    (Institut Pasteur)

  • Félix A. Rey

    (Structural Virology Unit, Institut Pasteur)

Abstract

Rabies virus (RABV) causes fatal encephalitis in more than 59,000 people yearly. Upon the bite of an infected animal, the development of clinical disease can be prevented with post-exposure prophylaxis (PEP), which includes the administration of Rabies immunoglobulin (RIG). However, the high cost and limited availability of serum-derived RIG severely hamper its wide use in resource-limited countries. A safe low-cost alternative is provided by using broadly neutralizing monoclonal antibodies (bnAbs). Here we report the X-ray structure of one of the most potent and most broadly reactive human bnAbs, RVC20, in complex with its target domain III of the RABV glycoprotein (G). The structure reveals that the RVC20 binding determinants reside in a highly conserved surface of G, rationalizing its broad reactivity. We further show that RVC20 blocks the acid-induced conformational change required for membrane fusion. Our results may guide the future development of direct antiviral small molecules for Rabies treatment.

Suggested Citation

  • Jan Hellert & Julian Buchrieser & Florence Larrous & Andrea Minola & Guilherme Dias Melo & Leah Soriaga & Patrick England & Ahmed Haouz & Amalio Telenti & Olivier Schwartz & Davide Corti & Hervé Bourh, 2020. "Structure of the prefusion-locking broadly neutralizing antibody RVC20 bound to the rabies virus glycoprotein," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14398-7
    DOI: 10.1038/s41467-020-14398-7
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    Cited by:

    1. Dan Fu & Wenming Wang & Yan Zhang & Fan Zhang & Pinyi Yang & Chun Yang & Yufei Tian & Renqi Yao & Jingwu Jian & Zixian Sun & Nan Zhang & Zhiyu Ni & Zihe Rao & Lei Zhao & Yu Guo, 2024. "Self-assembling nanoparticle engineered from the ferritinophagy complex as a rabies virus vaccine candidate," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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