Evidence map›Paper›PMID 28148786›Full record

ArticleJournal of virology2017

Neurovirulent Murine Coronavirus JHM.SD Uses Cellular Zinc Metalloproteases for Virus Entry and Cell-Cell Fusion.

Judith M Phillips, Tom Gallagher, Susan R Weiss

2 registry-linked trialsAbstract read
In one paragraph

Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 43 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 2 pooled it
6.3field-weighted citation impact, top 3% 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.

NCT04420260 nacompletednot on this mapstarted 2021, after this paper: background citation

Scheme of Primary Prevention of Infection by COVID-19, in Workers: Phase II Controlled Clinical Trial, to be Carried Out in Medellín-Antioquia

TypeinterventionalSponsorUnidad de Investigación Genética MolecularRan2021 to 2021Enrolled152ConditionsCOVIDArmsGroup A: oropharygeal spray and immunostimulant emulsion, Group D:Placebo oropharyngeal spray + Placebo taken PO
NCT04729140 phase4unknown statusnot on this mapstarted 2020, after this paper: background citation

A Randomized Double-blinded Placebo-controlled Outpatient Clinical Trial in High Risk Population Confirmed COVID-19 Patients Using Ivermectin and Doxycycline to Prevent COVID-19 Illness-related Hospitalization (COVIVER-OUT PLUS)

TypeinterventionalSponsorMax Health, Subsero HealthRan2020 to 2022Enrolled150ConditionsCovid19ArmsIvermectin Tablets, Doxycycline Tablets, Placebo
3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Repurposing of Tetracyclines for COVID-19 Neurological and Neuropsychiatric Manifestations: A Valid Option to Control SARS-CoV-2-Associated Neuroinflammation?Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021
    Article
  20. Review
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

3 authors at 2 institutions in 1 country.

Judith M PhillipsDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA jphil@upenn.edu.
Tom GallagherDepartment of Microbiology and Immunology, Loyola University Medical Center, Maywood, Illinois, USA.
Susan R WeissDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID http://orcid.org/0000-0002-8155-4528
University of Pennsylvania · USLoyola University Medical Center · US

Funding

Mechanisms of Neuronal Spread of Neurotropic Mouse Hepatitis VirusK08AI098503 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI PHILLIPS, JUDITH M · 2012 to 2016
$658k
NIAID NIH HHS K08 AI098503
6 · The paper itself

Abstract

The coronavirus (CoV) S protein requires cleavage by host cell proteases to mediate virus-cell and cell-cell fusion. Many strains of the murine coronavirus mouse hepatitis virus (MHV) have distinct, S-dependent organ and tissue tropisms despite using a common receptor, suggesting that they employ different cellular proteases for fusion. In support of this hypothesis, we found that inhibition of endosomal acidification only modestly decreased entry, and overexpression of the cell surface protease TMPRSS2 greatly enhanced entry, of the highly neurovirulent MHV strain JHM.SD relative to their effects on the reference strain, A59. However, TMPRSS2 overexpression decreased MHV structural protein expression, release of infectious particles, and syncytium formation, and endogenous serine protease activity did not contribute greatly to infection. We therefore investigated the importance of other classes of cellular proteases and found that inhibition of matrix metalloproteinase (MMP)- and a disintegrin and metalloprotease (ADAM)-family zinc metalloproteases markedly decreased both entry and cell-cell fusion. Suppression of virus by metalloprotease inhibition varied among tested cell lines and MHV S proteins, suggesting a role for metalloprotease use in strain-dependent tropism. We conclude that zinc metalloproteases must be considered potential contributors to coronavirus fusion.

Indexed as

Cell FusionHost-Pathogen InteractionsVirus InternalizationAnimalsMetalloproteasesMiceMurine hepatitis virusMetalloproteasescoronavirusmembrane fusionmetalloproteaseTMPRSS2virus entry

Identifiers

PMID28148786
PMCPMC5375694
OpenAlexW2584540405

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.