Evidence map›Paper›PMID 21799008›Full record

ArticleThe Journal of biological chemistry2011

Premature activation of the paramyxovirus fusion protein before target cell attachment with corruption of the viral fusion machinery.

Shohreh F Farzan, Laura M Palermo, Christine C Yokoyama, Gianmarco Orefice, Micaela Fornabaio, Aurijit Sarkar, Glen E Kellogg, Olga Greengard, Matteo Porotto, Anne Moscona

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

33 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
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  5. The Efficiency of p27 Cleavage duringJournal of virology · 2023
    Article
  6. Review
  7. Antivirals targeting paramyxovirus membrane fusion.Current opinion in virology · 2021
    Review
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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

10 authors at 2 institutions in 1 country.

Shohreh F FarzanDepartments of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021.
Laura M PalermoDepartments of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021.
Christine C YokoyamaDepartments of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021.
Gianmarco OreficeDepartments of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021.
Micaela FornabaioDepartment of Medicinal Chemistry and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia, 23298-0540.
Aurijit SarkarDepartment of Medicinal Chemistry and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia, 23298-0540.
Glen E KelloggDepartment of Medicinal Chemistry and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia, 23298-0540.
Olga GreengardDepartments of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021; Department of Pediatrics, Mount Sinai School of Medicine, New York, New York 10029.
Matteo PorottoDepartments of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021.
Anne MosconaDepartments of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021. Electronic address: anm2047@med.cornell.edu.
Cornell University · USVirginia Commonwealth University · US

Funding

Viral Pathogenesis and TherapeuticsU54AI057158 · NIAID · WADSWORTH CENTER · PI LEVY, DAVID E · 2003 to 2014
$100.8M
Molecular basis for paramyxovirus entryR01AI031971 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOSCONA, ANNE · 1998 to 2016
$6.6M
Bioengineering protocells for a new class of viral vaccinesR21EB011707 · NIBIB · WEILL MEDICAL COLL OF CORNELL UNIV · PI POROTTO, MATTEO · 2011 to 2012
$465k
Novel brain-penetrant fusion inhibitors for control of CNS infection.R21NS076385 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI POROTTO, MATTEO · 2011 to 2012
$443k
NIAID NIH HHS R01 AI031971NIAID NIH HHS R01AI31971NIAID NIH HHS U54 AI057158NIAID NIH HHS U54AI057158NIBIB NIH HHS R21 EB011707NIBIB NIH HHS R21EB011707NIGMS NIH HHS R01GM017894NINDS NIH HHS R21 NS076385
6 · The paper itself

Abstract

Paramyxoviruses, including the childhood pathogen human parainfluenza virus type 3, enter host cells by fusion of the viral and target cell membranes. This fusion results from the concerted action of its two envelope glycoproteins, the hemagglutinin-neuraminidase (HN) and the fusion protein (F). The receptor-bound HN triggers F to undergo conformational changes that render it competent to mediate fusion of the viral and cellular membranes. We proposed that, if the fusion process could be activated prematurely before the virion reaches the target host cell, infection could be prevented. We identified a small molecule that inhibits paramyxovirus entry into target cells and prevents infection. We show here that this compound works by an interaction with HN that results in F-activation prior to receptor binding. The fusion process is thereby prematurely activated, preventing fusion of the viral membrane with target cells and precluding viral entry. This first evidence that activation of a paramyxovirus F can be specifically induced before the virus contacts its target cell suggests a new strategy with broad implications for the design of antiviral agents.

Indexed as

AdsorptionAnimalsAntiviral AgentsChlorocebus aethiopsDose-Response Relationship, DrugEpithelial CellsHN ProteinHumansMembrane FusionModels, ChemicalNeuraminidaseProtein ConformationViral Fusion ProteinsViral ProteinsAntiviral AgentsHN ProteinNeuraminidaseViral Fusion ProteinsViral Proteins

Identifiers

PMID21799008
PMCPMC3207398
OpenAlexW2010145969

What OpenQuestion holds

Textmetadata
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.