Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun 27;15(1):5458.
doi: 10.1038/s41467-024-49757-1.

Structural basis for potent neutralization of human respirovirus type 3 by protective single-domain camelid antibodies

Nicole V Johnson #  1 , Revina C van Scherpenzeel #  2 , Mark J G Bakkers  3   4 , Ajit R Ramamohan  1 , Daan van Overveld  3 , Lam Le  3 , Johannes P M Langedijk  3   4 , Joost A Kolkman  2 , Jason S McLellan  5
Affiliations
Free PMC article

Structural basis for potent neutralization of human respirovirus type 3 by protective single-domain camelid antibodies

Nicole V Johnson et al. Nat Commun. .
Free PMC article

Abstract

Respirovirus 3 is a leading cause of severe acute respiratory infections in vulnerable human populations. Entry into host cells is facilitated by the attachment glycoprotein and the fusion glycoprotein (F). Because of its crucial role, F represents an attractive therapeutic target. Here, we identify 13 F-directed heavy-chain-only antibody fragments that neutralize recombinant respirovirus 3. High-resolution cryo-EM structures of antibody fragments bound to the prefusion conformation of F reveal three distinct, previously uncharacterized epitopes. All three antibody fragments bind quaternary epitopes on F, suggesting mechanisms for neutralization that may include stabilization of the prefusion conformation. Studies in cotton rats demonstrate the prophylactic efficacy of these antibody fragments in reducing viral load in the lungs and nasal passages. These data highlight the potential of heavy-chain-only antibody fragments as effective interventions against respirovirus 3 infection and identify neutralizing epitopes that can be targeted for therapeutic development.

PubMed Disclaimer

Similar articles

See all similar articles

References

    1. Nature. 1993 Jun 3;363(6428):446-8 - PubMed
    1. Virology. 1995 Jun 1;209(2):457-69 - PubMed
    1. Sci Transl Med. 2021 Nov 24;13(621):eabi7826 - PubMed
    1. MAbs. 2021 Jan-Dec;13(1):1912884 - PubMed
    1. Protein Sci. 2011 Jul;20(7):1196-207 - PubMed

LinkOut - more resources

-