Evidence map›Paper›PMID 34981051›Full record

ArticlebioRxiv : the preprint server for biology2021

A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors.

K Y Chen, T Krischuns, L Ortega Varga, E Harigua-Souiai, S Paisant, A Zettor, J Chiaravalli, D Courtney, A O'Brien, S C Baker and 5 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 5 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 3 countries.

K Y ChenRNA Biology and Influenza Virus Unit, Institut Pasteur, CNRS UMR3569, Université de Paris, Paris, France.
T KrischunsRNA Biology and Influenza Virus Unit, Institut Pasteur, CNRS UMR3569, Université de Paris, Paris, France.
L Ortega VargaStructural Bioinformatics Unit, Institut Pasteur, Université de Paris, Paris, France.
E Harigua-SouiaiLaboratory of Molecular Epidemiology and Experimental Pathology - LR16IPT04, Institut Pasteur de Tunis, Université de Tunis El Manar, Tunis, Tunisia.
S PaisantRNA Biology and Influenza Virus Unit, Institut Pasteur, CNRS UMR3569, Université de Paris, Paris, France.
A ZettorChemogenomic and Biological Screening Platform, Institut Pasteur, Université de Paris, Paris, France.
J ChiaravalliChemogenomic and Biological Screening Platform, Institut Pasteur, Université de Paris, Paris, France.
D CourtneyRNA Biology and Influenza Virus Unit, Institut Pasteur, CNRS UMR3569, Université de Paris, Paris, France.
A O'BrienDepartment of Microbiology and Immunology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA.
S C BakerDepartment of Microbiology and Immunology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA.
C IselRNA Biology and Influenza Virus Unit, Institut Pasteur, CNRS UMR3569, Université de Paris, Paris, France.
F AgouChemogenomic and Biological Screening Platform, Institut Pasteur, Université de Paris, Paris, France.
Y JacobMolecular Genetics of RNA Viruses, Institut Pasteur, CNRS UMR3569, Université de Paris, Paris, France.
A BlondelStructural Bioinformatics Unit, Institut Pasteur, Université de Paris, Paris, France.
N NaffakhRNA Biology and Influenza Virus Unit, Institut Pasteur, CNRS UMR3569, Université de Paris, Paris, France.
Centre National de la Recherche Scientifique · FRInstitut Pasteur · FRLoyola University Chicago · USTunis University · TN

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
Investigating Interferon Antagonists in Delaying Innate Immune Responses to SARS-CoV-2R01AI159945 · NIAID · LOYOLA UNIVERSITY CHICAGO · PI BAKER, SUSAN C. · 2021 to 2025
$4.0M
NIAID NIH HHS R01 AI085089NIAID NIH HHS R01 AI159945
6 · The paper itself

Abstract

Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for high-throughput screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified four molecules, including the broad-spectrum antiviral merimepodib/VX-497, which show anti-nsp5 activity and inhibit SARS-CoV-2 replication in A549-ACE2 cells with IC

Identifiers

PMID34981051
PMCPMC8722588
OpenAlexW4200274066

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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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.