Evidence map›Paper›PMID 24503068›Full record

ArticleVirology2014

MERS-CoV papain-like protease has deISGylating and deubiquitinating activities.

Anna M Mielech, Andy Kilianski, Yahira M Baez-Santos, Andrew D Mesecar, Susan C Baker

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04420260 (Scheme of Primary Prevention of Infection by COVID-19, in Workers), which is not on this map. Cited by 152 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
152citing papers in PubMed, 1 pooled it
6.2field-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
3 · Its place in the literature

Who cites it

152 citing papers in PubMed, 1 synthesis or guideline pooled it, 240 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Anti-interferon armamentarium of human coronaviruses.Cellular and molecular life sciences : CMLS · 2025
    Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
  14. Article
  15. Article
  16. An expanded lexicon for the ubiquitin code.Nature reviews. Molecular cell biology · 2023
    Review
  17. Computer-aided drug design for the pain-like protease (PLBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023
    Article
  18. Article
  19. Review
  20. A Method to Monitor Activity of SARS-CoV-2 Nsp3 from Cells.Methods in molecular biology (Clifton, N.J.) · 2023
    Article

92 more citing papers are in PubMed but not listed here.

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

5 authors at 2 institutions in 1 country.

Anna M MielechDepartment Microbiology and Immunology, Loyola University of Chicago, Stritch School of Medicine, 2160 S. First Ave., Maywood, IL 60153, USA.
Andy KilianskiDepartment Microbiology and Immunology, Loyola University of Chicago, Stritch School of Medicine, 2160 S. First Ave., Maywood, IL 60153, USA.
Yahira M Baez-SantosDepartment of Biological Sciences, Purdue University, 240 S. Martin Jischke Drive, West Lafayette, IN 47907, USA.
Andrew D MesecarDepartment of Biological Sciences, Purdue University, 240 S. Martin Jischke Drive, West Lafayette, IN 47907, USA.
Susan C BakerDepartment Microbiology and Immunology, Loyola University of Chicago, Stritch School of Medicine, 2160 S. First Ave., Maywood, IL 60153, USA. Electronic address: sbaker1@lumc.edu.
Loyola University Chicago · USPurdue University West Lafayette · US

Funding

Mechanisms of viral proteases in coronavirus replication and pathogenesisR01AI085089 · NIAID · LOYOLA UNIVERSITY CHICAGO · PI BAKER, SUSAN C., MESECAR, ANDREW D · 2010 to 2019
$6.8M
Experimental Immunology Training GrantT32AI007508 · NIAID · LOYOLA UNIVERSITY CHICAGO · PI KNIGHT, KATHERINE L. · 1997 to 2022
$4.0M
NIAID NIH HHS R01 AI085089NIAID NIH HHS R01AI085089NIAID NIH HHS T32 AI007508NIAID NIH HHS T32AI512795
6 · The paper itself

Abstract

Coronaviruses encode papain-like proteases (PLpro) that are often multifunctional enzymes with protease activity to process the viral replicase polyprotein and deubiquitinating (DUB)/deISGylating activity, which is hypothesized to modify the innate immune response to infection. Here, we investigate the predicted DUB activity of the PLpro domain of the recently described Middle East Respiratory Syndrome Coronavirus (MERS-CoV). We found that expression of MERS-CoV PLpro reduces the levels of ubiquitinated and ISGylated host cell proteins; consistent with multifunctional PLpro activity. Further, we compared the ability of MERS-CoV PLpro and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) PLpro to block innate immune signaling of proinflammatory cytokines. We show that expression of SARS-CoV and MERS-CoV PLpros blocks upregulation of cytokines CCL5, IFN-β and CXCL10 in stimulated cells. Overall these results indicate that the PLpro domains of MERS-CoV and SARS-CoV have the potential to modify the innate immune response to viral infection and contribute to viral pathogenesis.

Indexed as

Amino Acid SequenceCell LineCoronaviridaeCoronaviridae InfectionsCytokinesGlycosylationHumansMolecular Sequence DataPapainProtein Structure, TertiarySevere acute respiratory syndrome-related coronavirusUbiquitinationUbiquitinsViral ProteinsCytokinesISG15 protein, humanPapainUbiquitinsViral ProteinsdeISGylating activityDUB activityISG15MERS-CoVPLproUbiquitin

Identifiers

PMID24503068
PMCPMC3957432
OpenAlexW2060027762

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.