Evidence map›Paper›PMID 38351001›Full record

ArticleNature communications2024

A general computational design strategy for stabilizing viral class I fusion proteins.

Karen J Gonzalez, Jiachen Huang, Miria F Criado, Avik Banerjee, Stephen M Tompkins, Jarrod J Mousa, Eva-Maria Strauch

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Stabilized mosaic hemagglutinin immunogens as novel universal influenza virus vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Review
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  8. Article
  9. Article
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  11. Review
  12. Introduction to Respiratory Syncytial Virus.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  13. Article
  14. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Karen J GonzalezInstitute of Bioinformatics, Franklin College of Arts and Sciences, University of Georgia, Athens, GA, 30602, USA.ORCID 0000-0002-5587-3613
Jiachen HuangDepartment of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA.
Miria F CriadoCenter for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA.
Avik BanerjeeDepartment of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA.
Stephen M TompkinsDepartment of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA.ORCID 0000-0002-1523-5588
Jarrod J MousaDepartment of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA.ORCID 0000-0003-4709-2478
Eva-Maria StrauchInstitute of Bioinformatics, Franklin College of Arts and Sciences, University of Georgia, Athens, GA, 30602, USA. evas@wustl.edu.ORCID 0000-0001-7382-747X
University of Georgia · US

Funding

NIAID Centers of Excellence for Influenza Research and Response: Universal Influenza Vaccine Research Activities75N93021C00018 · NIAID · UNIVERSITY OF GEORGIA · PI TOMPKINS, S. MARK · 2021 to 2025
$21.6M
Structural and mechanistic insights into antibody neutralization of human metapneumovirusR01AI143865 · NIAID · UNIVERSITY OF GEORGIA · PI MOUSA, JARROD · 2019 to 2023
$3.0M
Design of Antivirals and Immunogens Targeting ParamyxovirusesR01AI140245 · NIAID · WASHINGTON UNIVERSITY · PI STRAUCH, EVA-MARIA · 2018 to 2023
$1.9M
NIAID NIH HHS 75N93021C00018NIAID NIH HHS HHSN272201400004CNIAID NIH HHS R01 AI140245NIAID NIH HHS R01 AI143865
6 · The paper itself

Abstract

Many pathogenic viruses rely on class I fusion proteins to fuse their viral membrane with the host cell membrane. To drive the fusion process, class I fusion proteins undergo an irreversible conformational change from a metastable prefusion state to an energetically more stable postfusion state. Mounting evidence underscores that antibodies targeting the prefusion conformation are the most potent, making it a compelling vaccine candidate. Here, we establish a computational design protocol that stabilizes the prefusion state while destabilizing the postfusion conformation. With this protocol, we stabilize the fusion proteins of the RSV, hMPV, and SARS-CoV-2 viruses, testing fewer than a handful of designs. The solved structures of these designed proteins from all three viruses evidence the atomic accuracy of our approach. Furthermore, the humoral response of the redesigned RSV F protein compares to that of the recently approved vaccine in a mouse model. While the parallel design of two conformations allows the identification of energetically sub-optimal positions for one conformation, our protocol also reveals diverse molecular strategies for stabilization. Given the clinical significance of viruses using class I fusion proteins, our algorithm can substantially contribute to vaccine development by reducing the time and resources needed to optimize these immunogens.

Indexed as

VaccinesViral Fusion ProteinsAnimalsAntibodies, NeutralizingAntibodies, ViralMiceProtein ConformationAntibodies, NeutralizingAntibodies, ViralVaccinesViral Fusion Proteins

Identifiers

PMID38351001
PMCPMC10864359
OpenAlexW4391776152

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.