Evidence map›Paper›PMID 35597097›Full record

ArticleBioorganic & medicinal chemistry2022

Design, synthesis and evaluation of inhibitors of the SARS-CoV-2 nsp3 macrodomain.

Lavinia M Sherrill, Elva E Joya, AnnMarie Walker, Anuradha Roy, Yousef M Alhammad, Moriama Atobatele, Sarah Wazir, George Abbas, Patrick Keane, Junlin Zhuo and 5 more

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

Article in Bioorganic & medicinal chemistry, 2022. 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
3.9field-weighted citation impact, top 6% 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, 27 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Lavinia M SherrillMcDaniel College, Department of Chemistry, 2 College Hill, Westminster, MD 21157, USA.
Elva E JoyaMcDaniel College, Department of Chemistry, 2 College Hill, Westminster, MD 21157, USA.
AnnMarie WalkerMcDaniel College, Department of Chemistry, 2 College Hill, Westminster, MD 21157, USA.
Anuradha RoyInfectious Disease Assay Development Laboratory/HTS, University of Kansas, Lawrence, KS 66047, USA.
Yousef M AlhammadDepartment of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
Moriama AtobateleInfectious Disease Assay Development Laboratory/HTS, University of Kansas, Lawrence, KS 66047, USA.
Sarah WazirFaculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland.
George AbbasMcDaniel College, Department of Chemistry, 2 College Hill, Westminster, MD 21157, USA.
Patrick KeaneMcDaniel College, Department of Chemistry, 2 College Hill, Westminster, MD 21157, USA.
Junlin ZhuoDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Anthony K L LeungDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Oncology, McKusick-Nathans Department of Genetic Medicine and Department of Molecular Biology and Genetics, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
David K JohnsonMolecular Graphics and Modeling Laboratory and the Computational Chemical Biology Core, University of Kansas, Lawrence, KS 66047, USA.
Lari LehtiöFaculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland.
Anthony R FehrDepartment of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA. Electronic address: arfehr@ku.edu.
Dana FerrarisMcDaniel College, Department of Chemistry, 2 College Hill, Westminster, MD 21157, USA. Electronic address: dferraris@mcdaniel.edu.
McDaniel College · USUniversity of Kansas · USUniversity of Oulu · FIJohns Hopkins Medicine · USJohns Hopkins University · US

Funding

RADx-UP: Improving the Response of Local Urban and Rural Communities to Disparities in Covid-19 TestingUL1TR002366 · NCATS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Mario Castro, JAMES STEVEN LEEDER · 2017 to 2026
$44.3M
Synthetic Chemical Biology CoreP20GM113117 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI OROZCO, ROBIN C. · 2016 to 2025
$23.9M
Protein Structure Laboratory P30GM110761 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI HANZLIK, ROBERT P · 2014 to 2018
$5.6M
NCATS NIH HHS UL1 TR002366NIGMS NIH HHS P20 GM113117NIGMS NIH HHS P30 GM110761
6 · The paper itself

Abstract

A series of amino acid based 7H-pyrrolo[2,3-d]pyrimidines were designed and synthesized to discern the structure activity relationships against the SARS-CoV-2 nsp3 macrodomain (Mac1), an ADP-ribosylhydrolase that is critical for coronavirus replication and pathogenesis. Structure activity studies identified compound 15c as a low-micromolar inhibitor of Mac1 in two ADP-ribose binding assays. This compound also demonstrated inhibition in an enzymatic assay of Mac1 and displayed a thermal shift comparable to ADPr in the melting temperature of Mac1 supporting binding to the target protein. A structural model reproducibly predicted a binding mode where the pyrrolo pyrimidine forms a hydrogen bonding network with Asp

Indexed as

COVID-19 Drug TreatmentSARS-CoV-2Adenosine Diphosphate RiboseAmidesHumansProtein DomainsAdenosine Diphosphate RiboseAmidesADP-ribosylationCoronavirusCOVID-19Nsp3 macrodomain inhibitorsSARS-CoV-2

Identifiers

PMID35597097
PMCPMC9093066
OpenAlexW4280494607

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.