Evidence map›Paper›PMID 23986593›Full record

ArticleJournal of virology2013

Assessing activity and inhibition of Middle East respiratory syndrome coronavirus papain-like and 3C-like proteases using luciferase-based biosensors.

Andy Kilianski, Anna M Mielech, Xufang Deng, Susan C Baker

Abstract read
In one paragraph

Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 1 pooled it
7.1field-weighted citation impact, top 2% 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

99 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Utilizing sinapic acid as an inhibitory antiviral agent against MERS-CoV PLpro.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Screening and identification of potential MERS-CoV papain-like protease (PLpro) inhibitors; Steady-state kinetic and Molecular dynamic studies.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Potential Inhibitors of SARS-CoV-2 fromTurkish journal of pharmaceutical sciences · 2022
    Article
  18. Review
  19. Article
  20. A genetically encoded BRET-based SARS-CoV-2 MCommunications chemistry · 2022
    Article

39 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

4 authors at 2 institutions in 1 country.

Andy KilianskiDepartment of Microbiology and Immunology, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois, USA.
Anna M Mielech
Xufang Deng
Susan C Baker
University of Chicago · USLoyola University Chicago · 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 T32 AI512795
6 · The paper itself

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with an outbreak of more than 90 cases of severe pneumonia with high mortality (greater than 50%). To date, there are no antiviral drugs or specific therapies to treat MERS-CoV. To rapidly identify potential inhibitors of MERS-CoV replication, we expressed the papain-like protease (PLpro) and the 3-chymotrypsin-like protease (3CLpro) from MERS-CoV and developed luciferase-based biosensors to monitor protease activity in cells. We show that the expressed MERS-CoV PLpro recognizes and processes the canonical CoV-PLpro cleavage site RLKGG in the biosensor. However, existing CoV PLpro inhibitors were unable to block MERS-CoV PLpro activity, likely due to the divergence of the amino acid sequence in the drug binding site. To investigate MERS-CoV 3CLpro activity, we expressed the protease in context with flanking nonstructural protein 4 (nsp4) and the amino-terminal portion of nsp6 and detected processing of the luciferase-based biosensors containing the canonical 3CLpro cleavage site VRLQS. Importantly, we found that a small-molecule inhibitor that blocks replication of severe acute respiratory syndrome (SARS) CoV and murine CoV also inhibits the activity of MERS-CoV 3CLpro. Overall, the protease expression and biosensor assays developed here allow for rapid evaluation of viral protease activity and the identification of protease inhibitors. These biosensor assays can now be used to screen for MERS-CoV-specific or broad-spectrum coronavirus PLpro and 3CLpro inhibitors.

Indexed as

3C Viral ProteasesAntiviral AgentsBiosensing TechniquesCell LineCoronavirusCysteine EndopeptidasesDrug Evaluation, PreclinicalGenes, ReporterHumansLuciferasesProtease InhibitorsViral Proteins3C Viral ProteasesAntiviral AgentsCysteine EndopeptidasesLuciferasesProtease InhibitorsViral Proteins

Identifiers

PMID23986593
PMCPMC3807373
OpenAlexW2103616039

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.