Evidence map›Paper›PMID 37770002›Full record

ArticleBioorganic & medicinal chemistry letters2023

SARS-CoV-2 papain-like protease (PLpro) inhibitory and antiviral activity of small molecule derivatives for drug leads.

Arun K Ghosh, Dana Shahabi, Mackenzie E C Imhoff, Satish Kovela, Ashish Sharma, Shin-Ichiro Hattori, Nobuyo Higashi-Kuwata, Hiroaki Mitsuya, Andrew D Mesecar

Open access · greenAbstract read
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

6 citing papers in PubMed, 10 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

9 authors at 2 institutions in 2 countries.

Arun K GhoshDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907 USA. Electronic address: akghosh@purdue.edu.
Dana ShahabiDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907 USA.
Mackenzie E C ImhoffDepartment of Biochemistry, Purdue University, West Lafayette, IN 47907 USA.
Satish KovelaDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907 USA.
Ashish SharmaDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907 USA.
Shin-Ichiro HattoriDepartment of Refractory Viral Diseases, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655 Japan.
Nobuyo Higashi-KuwataDepartment of Refractory Viral Diseases, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655 Japan.
Hiroaki MitsuyaDepartment of Refractory Viral Diseases, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655 Japan; Department of Clinical Sciences, Kumamoto University Hospital, Kumamoto 860-8556 Japan; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch National Cancer Institute, Bethesda, MD 20892 USA.
Andrew D MesecarDepartment of Biological Sciences, Purdue University, West Lafayette, IN 47907 USA.
Purdue University West Lafayette · USNational Center for Global Health and Medicine · JP

Funding

Transgenic Mouse Core Facility Shared Resource (TMCF-SR)P30CA023168 · NCI · PURDUE UNIVERSITY WEST LAFAYETTE · PI ANDREW D MESECAR · 1985 to 2026
$43.4M
Protein Expression and PurificationP01AI060915 · NIAID · UNIVERSITY OF ILLINOIS AT CHICAGO · PI JOHNSON, MICHAEL E. · 2005 to 2009
$7.7M
SARS-CoV-2 protease inhibitors for treating COVID-19R01AI158649 · NIAID · PURDUE UNIVERSITY · PI ARUN K GHOSH, ANDREW D MESECAR · 2021 to 2026
$3.8M
Design & Synthesis of Nonpeptide Protease InhibitorsR01AI150466 · NIAID · PURDUE UNIVERSITY · PI ARUN K GHOSH · 2023 to 2026
$2.4M
Purdue University Molecular Biophysics Training ProgramT32GM132024 · NIGMS · PURDUE UNIVERSITY · PI Angeline Marie Lyon, John Tesmer · 2019 to 2026
$2.0M
Design & Synthesis of Nonpeptide Protease InhibitorsR37AI150466 · NIAID · PURDUE UNIVERSITY · PI GHOSH, ARUN K · 2019 to 2020
$969k
NCI NIH HHS P30 CA023168NIAID NIH HHS HHSN272201700060CNIAID NIH HHS P01 AI060915NIAID NIH HHS R01 AI150466NIAID NIH HHS R01 AI158649NIAID NIH HHS R37 AI150466NIGMS NIH HHS T32 GM132024
6 · The paper itself

Abstract

We report here the synthesis and biological evaluation of a series of small molecule SARS-CoV-2 PLpro inhibitors. We compared the activity of selected compounds in both SARS-CoV-1 and SARS-CoV-2 PLpro inhibitory and antiviral assays. We have synthesized and evaluated several new structural variants of previous leads against SARS-CoV-2 PLpro. The replacement of the carboxamide functionality with sulfonamide derivatives resulted in PLpro inhibitors with potent PLpro inhibitory and antiviral activity in VeroE6 cells similar to GRL0617. To obtain molecular insight, we created an optimized model of a potent sulfonamide derivative in the SARS-CoV-2 PLpro active site.

Indexed as

COVID-19SARS-CoV-2Antiviral AgentsCoronavirus Papain-Like ProteasesHumansSulfonamidesAntiviral AgentsCoronavirus Papain-Like Proteasespapain-like protease, SARS-CoV-2SulfonamidesAntiviralCovid-19InhibitorSARS-CoV-2 proteaseSynthesis

Identifiers

PMID37770002
PMCPMC10842477
OpenAlexW4387035676

What OpenQuestion holds

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LicenceTDM
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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.