Evidence map›Paper›PMID 33910954›Full record

ArticleJournal of virology2021

Inhibitors of Coronavirus 3CL Proteases Protect Cells from Protease-Mediated Cytotoxicity.

Samuel J Resnick, Sho Iketani, Seo Jung Hong, Arie Zask, Hengrui Liu, Sungsoo Kim, Schuyler Melore, Fang-Yu Lin, Manoj S Nair, Yaoxing Huang and 8 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.7field-weighted citation impact, top 8% 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

28 citing papers in PubMed, 49 citations in OpenAlex.

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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

18 authors at 4 institutions in 1 country.

Samuel J ResnickDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
Sho IketaniAaron Diamond AIDS Research Center, Columbia University Irving Medical Center, New York, New York, USA.
Seo Jung HongDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
Arie ZaskDepartment of Biological Sciences, Columbia University, New York, New York, USA.
Hengrui LiuDepartment of Chemistry, Columbia University, New York, New York, USA.
Sungsoo KimDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
Schuyler MeloreDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
Fang-Yu LinWuXi AppTec, Cambridge, Massachusetts, USA.
Manoj S NairAaron Diamond AIDS Research Center, Columbia University Irving Medical Center, New York, New York, USA.
Yaoxing HuangAaron Diamond AIDS Research Center, Columbia University Irving Medical Center, New York, New York, USA.
Sumin LeeDepartment of Chemistry, Columbia University, New York, New York, USA.
Nicholas E S TayDepartment of Chemistry, Columbia University, New York, New York, USA.
Tomislav RovisDepartment of Chemistry, Columbia University, New York, New York, USA.
Hee Won YangDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
Li XingWuXi AppTec, Cambridge, Massachusetts, USA.
Brent R StockwellDepartment of Biological Sciences, Columbia University, New York, New York, USA.
David D HoAaron Diamond AIDS Research Center, Columbia University Irving Medical Center, New York, New York, USA.
Alejandro ChavezDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
Columbia University · USColumbia University Irving Medical Center · USAaron Diamond AIDS Research Center · USWuXi AppTec (United States) · US

Funding

Columbia University Graduate Training Program in Microbiology and ImmunologyT32AI106711 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Nicholas Arpaia, Uttiya Basu · 2014 to 2026
$2.1M
High-throughput disease modeling to uncover shared and unique characteristics among neurodegenerative diseasesF31NS111851 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI RESNICK, SAMUEL JACKSON · 2019 to 2020
$91k
HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) T32AI106711HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) F31NS111851NIAID NIH HHS T32 AI106711NINDS NIH HHS F31 NS111851
6 · The paper itself

Abstract

We describe a mammalian cell-based assay to identify coronavirus 3CL protease (3CLpro) inhibitors. This assay is based on rescuing protease-mediated cytotoxicity and does not require live virus. By enabling the facile testing of compounds across a range of 15 distantly related coronavirus 3CLpro enzymes, we identified compounds with broad 3CLpro-inhibitory activity. We also adapted the assay for use in compound screening and in doing so uncovered additional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CLpro inhibitors. We observed strong concordance between data emerging from this assay and those obtained from live-virus testing. The reported approach democratizes the testing of 3CLpro inhibitors by developing a simplified method for identifying coronavirus 3CLpro inhibitors that can be used by the majority of laboratories, rather than the few with extensive biosafety infrastructure. We identified two lead compounds, GC376 and compound 4, with broad activity against all 3CL proteases tested, including 3CLpro enzymes from understudied zoonotic coronaviruses.

Indexed as

Coronavirus 3C ProteasesCysteine Proteinase InhibitorsCOVID-19COVID-19 Drug TreatmentHEK293 CellsHumansSARS-CoV-2Coronavirus 3C ProteasesCysteine Proteinase Inhibitors3CL proteaseantiviral drugscell-based assaycoronavirusCOVID-19protease inhibitorsprotease-mediated cytotoxicitySARS-CoV-2zoonotic coronaviruses

Identifiers

PMID33910954
PMCPMC8223961
OpenAlexW3158489710

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.