Evidence map›Paper›PMID 34642689›Full record

ArticleResearch square2022

Potent and Selective Covalent Inhibition of the Papain-like Protease from SARS-CoV-2.

Brian Sanders, Suman Pokhrel, Audrey Labbe, Irimpan Mathews, Connor Cooper, Russell Davidson, Gwyndalyn Phillips, Kevin Weiss, Qiu Zhang, Hugh O'Neill and 23 more

Open access · greenAbstract readPreprint
In one paragraph

Article in Research square, 2022. 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, 13 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors at 10 institutions in 2 countries.

Brian SandersOak Ridge National Laboratory.ORCID 0000-0001-9754-1687
Suman PokhrelStanford University.ORCID 0000-0003-2258-8768
Audrey LabbeOak Ridge National Laboratory.ORCID 0000-0002-9802-665X
Irimpan MathewsSLAC National Accelerator Laboratory.ORCID 0000-0001-6254-3519
Connor CooperOak Ridge National Laboratory.ORCID 0000-0002-5527-9948
Russell DavidsonOak Ridge National Laboratory.ORCID 0000-0003-2364-4039
Gwyndalyn PhillipsOak Ridge National Laboratory.ORCID 0000-0001-5858-3825
Kevin WeissOak Ridge National Laboratory.ORCID 0000-0002-6486-8007
Qiu ZhangOak Ridge National Laboratory.ORCID 0000-0002-5506-4955
Hugh O'NeillOak Ridge National Laboratory.ORCID 0000-0003-2966-5527
Manat KaurStanford University.
Lori FerrinsNortheastern University.ORCID 0000-0001-8992-0919
Jurgen SchmidtLos Alamos National Laboratory.ORCID 0000-0002-8192-9940
Walter ReichardUniversity of Tennessee Health Science Center.
Surekha SurendranathanUniversity of Tennessee Health Science Center.
Jyothi ParvathareddyUniversity of Tennessee Health Science Center.
Lexi PhillipsUtah State University.
Christopher RainvilleProgenra Inc.
David SternerProgenra Inc.
Desigan KumaranBrookhaven National Laboratory.ORCID 0000-0002-6121-5350
Babak AndiBrookhaven National Laboratory.ORCID 0000-0002-7666-639X
Gyorgy BabniggArgonne National Laboratory.ORCID 0000-0002-9838-1803
Nigel MoriarrtyLawrence Berkeley National Laboratory.ORCID 0000-0001-8857-9464
Paul AdamsLawrence Berkeley Laboratory.ORCID 0000-0001-9333-8219
Andrzej JoachimiakUniversity of Chicago.ORCID 0000-0003-2535-6209
Brett HurstInstitute for Antiviral Research, Utah State University.ORCID 0000-0003-1025-5878
Suresh KumarProgenra.ORCID 0000-0002-1940-772X
Tauseef ButtProgenra.
Colleen JonssonUniversity of Tennessee Health Science Center.ORCID 0000-0002-2640-7672
Soichi WakatsukiStanford University.ORCID 0000-0001-5896-7968
Stephanie GalanieOak Ridge National Lab.ORCID 0000-0001-5712-2568
Martha HeadOak Ridge National Laboratory.ORCID 0000-0001-7452-4753
Jerry ParksOak Ridge National Laboratory.ORCID 0000-0002-3103-9333
Oak Ridge National Laboratory · USStanford University · USThe University of Texas Health Science Center at Houston · USBrookhaven National Laboratory · USLawrence Berkeley National Laboratory · USArgonne National Laboratory · USLos Alamos National Laboratory · USSLAC National Accelerator Laboratory · USUniversidad del Noreste · MXUniversity of Chicago · US

Funding

A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Ritimukta Sarangi · 2020 to 2026
$43.3M
NIAID NIH HHS HHSN272201700060CNIGMS NIH HHS P30 GM133894
6 · The paper itself

Abstract

Direct-acting antivirals are needed to combat coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The papain-like protease (PLpro) domain of Nsp3 from SARS-CoV-2 is essential for viral replication. In addition, PLpro dysregulates the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 protein (ISG15) from host proteins. As a result, PLpro is a promising target for inhibition by small-molecule therapeutics. Here we have designed a series of covalent inhibitors by introducing a peptidomimetic linker and reactive electrophile onto analogs of the noncovalent PLpro inhibitor GRL0617. The most potent compound inhibited PLpro with

Identifiers

PMID34642689
PMCPMC8509099
OpenAlexW3203035096

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.