Evidence map›Paper›PMID 31951396›Full record

ArticleJournal of the American Chemical Society2020

Structure-Guided Improvement of a Dual HPIV3/RSV Fusion Inhibitor.

Victor K Outlaw, Jennifer T Lemke, Yun Zhu, Samuel H Gellman, Matteo Porotto, Anne Moscona

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

15 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  10. Article
  11. Treatment of Respiratory Viral Coinfections.Epidemiologia (Basel, Switzerland) · 2022
    Article
  12. Antivirals targeting paramyxovirus membrane fusion.Current opinion in virology · 2021
    Review
  13. Article
  14. Article
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Victor K OutlawDepartment of Chemistry , University of Wisconsin , Madison , Wisconsin 53706 , United States.ORCID 0000-0001-7054-4204
Jennifer T LemkeDepartment of Chemistry , University of Wisconsin , Madison , Wisconsin 53706 , United States.
Yun ZhuDepartment of Pediatrics , Columbia University Medical Center , New York , New York 10032 , United States.
Samuel H GellmanDepartment of Chemistry , University of Wisconsin , Madison , Wisconsin 53706 , United States.ORCID 0000-0001-5617-0058
Matteo PorottoDepartment of Pediatrics , Columbia University Medical Center , New York , New York 10032 , United States.
Anne MosconaDepartment of Pediatrics , Columbia University Medical Center , New York , New York 10032 , United States.
Columbia University Irving Medical Center · US

Funding

Engineering protease-resistant alpha-beta peptides for broad-spectrum antiviralsR01AI114736 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOSCONA, ANNE · 2015 to 2019
$3.7M
Development of novel endosome-targeted Ebola virus entry inhibitors as antiviral agentsR01AI121349 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI POROTTO, MATTEO · 2016 to 2020
$3.2M
Structure-Guided Design of Peptidomimetic Inhibitors of Paramyxoviral FusionF32GM122263 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI OUTLAW, VICTOR KENNETH · 2017 to 2017
$57k
NIAID NIH HHS R01 AI114736NIAID NIH HHS R01 AI121349NIGMS NIH HHS F32 GM122263
6 · The paper itself

Abstract

Human parainfluenza virus 3 (HPIV3) and respiratory syncytial virus (RSV) are leading causes of lower respiratory tract infections. There are currently no vaccines or antiviral therapeutics to treat HPIV3 or RSV infections. We recently reported a peptide (VIQKI), derived from the C-terminal heptad repeat (HRC) domain of the HPIV3 fusion (F) glycoprotein that inhibits infection by both HPIV3 and RSV. The dual inhibitory activity of VIQKI is due to its unique ability to bind to the N-terminal heptad repeat (HRN) domains of both HPIV3 and RSV F, thereby preventing the native HRN-HRC interactions required for viral entry. Here we describe the structure-guided design of dual inhibitors of HPIV3 and RSV fusion with improved efficacy. We show that VIQKI derivatives possessing one (I456F) or two (I454F/I456F) phenylalanine substitutions near the N-terminus exhibit more stable assemblies with the RSV-HRN domain and enhanced antiviral efficacy against both HPIV3 and RSV infection. Cocrystal structures of the new Phe-substituted inhibitors coassembled with HPIV3 or RSV-HRN domains reveal that the I456F substitution makes intimate hydrophobic contact with the core trimers of both HPIV3 and RSV F.

Indexed as

Amino Acid SequenceAntiviral AgentsCrystallography, X-RayHydrophobic and Hydrophilic InteractionsMolecular StructureOligopeptidesParainfluenza Virus 3, HumanProtein ConformationRespiratory Syncytial Virus, HumanVirus InternalizationAntiviral AgentsOligopeptides

Identifiers

PMID31951396
PMCPMC7047708
OpenAlexW3000250614

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.