Evidence map›Paper›PMID 37025664›Full record

ArticleRSC advances2023

A covalent inhibitor targeting the papain-like protease from SARS-CoV-2 inhibits viral replication.

Hesong Han, Albert Vallejo Gracia, Joachim J Røise, Lydia Boike, Kristoffer Leon, Ursula Schulze-Gahmen, Michael R Stentzel, Teena Bajaj, Dake Chen, I-Che Li and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in RSC advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

3 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
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.

Hesong HanDepartment of Bioengineering, University of California at Berkeley Berkeley CA USA nmurthy@berkeley.edu.ORCID https://orcid.org/0000-0001-5545-5238
Albert Vallejo GraciaGladstone Institute of Virology, Gladstone Institutes San Francisco CA USA melanie.ott@gladstone.ucsf.edu.
Joachim J RøiseDepartment of Bioengineering, University of California at Berkeley Berkeley CA USA nmurthy@berkeley.edu.ORCID https://orcid.org/0000-0002-1794-7570
Lydia BoikeDepartment of Chemistry, University of California Berkeley CA USA.
Kristoffer LeonGladstone Institute of Virology, Gladstone Institutes San Francisco CA USA melanie.ott@gladstone.ucsf.edu.
Ursula Schulze-GahmenGladstone Institute of Virology, Gladstone Institutes San Francisco CA USA melanie.ott@gladstone.ucsf.edu.
Michael R StentzelDepartment of Bioengineering, University of California at Berkeley Berkeley CA USA nmurthy@berkeley.edu.
Teena BajajGraduate Program of Comparativ Biochemistry, University of California at Berkeley Berkeley CA USA.
Dake ChenDepartment of Bioengineering, University of California at Berkeley Berkeley CA USA nmurthy@berkeley.edu.
I-Che LiDepartment of Bioengineering, University of California at Berkeley Berkeley CA USA nmurthy@berkeley.edu.ORCID https://orcid.org/0000-0002-5819-8094
Maomao HeDepartment of Bioengineering, University of California at Berkeley Berkeley CA USA nmurthy@berkeley.edu.ORCID https://orcid.org/0000-0002-7682-1142
Kamyar BehrouziMolecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California Berkeley CA USA.
Zahra KhodabakhshiMolecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California Berkeley CA USA.
Daniel K NomuraDepartment of Chemistry, University of California Berkeley CA USA.ORCID https://orcid.org/0000-0003-1614-8360
Mohammad R K MofradMolecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California Berkeley CA USA.ORCID https://orcid.org/0000-0001-7004-4859
G Renuka KumarGladstone Institute of Virology, Gladstone Institutes San Francisco CA USA melanie.ott@gladstone.ucsf.edu.
Melanie OttGladstone Institute of Virology, Gladstone Institutes San Francisco CA USA melanie.ott@gladstone.ucsf.edu.
Niren MurthyDepartment of Bioengineering, University of California at Berkeley Berkeley CA USA nmurthy@berkeley.edu.ORCID https://orcid.org/0000-0002-7815-7337
University of California, Berkeley · USGladstone Institutes · USInnovative Genomics Institute · USLawrence Berkeley National Laboratory · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Covalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 have great potential as antivirals, but their non-specific reactivity with thiols has limited their development. In this report, we performed an 8000 molecule electrophile screen against PLpro and identified an α-chloro amide fragment, termed compound 1, which inhibited SARS-CoV-2 replication in cells, and also had low non-specific reactivity with thiols. Compound 1 covalently reacts with the active site cysteine of PLpro, and had an IC50 of 18 μM for PLpro inhibition. Compound 1 also had low non-specific reactivity with thiols and reacted with glutathione 1-2 orders of magnitude slower than other commonly used electrophilic warheads. Finally, compound 1 had low toxicity in cells and mice and has a molecular weight of only 247 daltons and consequently has great potential for further optimization. Collectively, these results demonstrate that compound 1 is a promising lead fragment for future PLpro drug discovery campaigns.

Identifiers

PMID37025664
PMCPMC10072198
OpenAlexW4362565985

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.