Evidence map›Paper›PMID 42439527›Full record

ArticleJournal of medicinal chemistry2026

X-ray Crystallography-Guided Design and Synthesis of Cyclopentyl Heteroaryl Carboxylic Acid-Based Inhibitors of the SARS-CoV-2 Nsp3 Macrodomain (Mac1).

Xinyu Wang, William T W Butler, James R Donald, Yuran Wang, Alice L Shaw, Marion Schuller, Daren Fearon, Jasmin C Aschenbrenner, Peter G Marples, Grant Watt and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2026. 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.

No citing paper in PubMed yet.

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

17 authors.

Xinyu WangDepartment of Chemistry, University of York, York YO10 5DD, U.K.ORCID 0000-0003-1115-7241
William T W ButlerDepartment of Chemistry, University of York, York YO10 5DD, U.K.ORCID 0000-0003-4581-4617
James R DonaldDepartment of Chemistry, University of York, York YO10 5DD, U.K.
Yuran WangDepartment of Chemistry, University of York, York YO10 5DD, U.K.
Alice L ShawDepartment of Chemistry, University of York, York YO10 5DD, U.K.
Marion SchullerSir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, U.K.
Daren FearonDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot Oxfordshire, U.K.
Jasmin C AschenbrennerDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot Oxfordshire, U.K.ORCID 0000-0002-4318-0481
Peter G MarplesDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot Oxfordshire, U.K.
Grant WattDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot Oxfordshire, U.K.
Yang LuSir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, U.K.
Simon C C LucasHit Discovery, Discovery Sciences, R&D, AstraZeneca, 1 Francis Crick Ave, Cambridge CB2 0AA, U.K.ORCID 0000-0002-9172-8739
Silvia BonomoHit Discovery, Discovery Sciences, R&D, AstraZeneca, 1 Francis Crick Ave, Cambridge CB2 0AA, U.K.ORCID 0000-0003-2394-2861
Jennifer E NelsonHit Discovery, Discovery Sciences, R&D, AstraZeneca, 1 Francis Crick Ave, Cambridge CB2 0AA, U.K.ORCID 0000-0002-3000-2993
Ivan AhelSir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, U.K.
Frank von DelftDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot Oxfordshire, U.K.
Peter O'BrienDepartment of Chemistry, University of York, York YO10 5DD, U.K.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mac1 is a conserved macrodomain enzyme in the nonstructural protein 3 (Nsp3) of SARS-CoV-2 and is part of the viral replication machinery. Mac1 is a target for small-molecule inhibitors that could ultimately enable new COVID-19 therapeutics to be developed. Here, we report the structure-guided design, synthesis, and Mac1 inhibition profiling of 25 analogues derived from a hit identified through crystallographic fragment screening. The heteroaryl group and scaffold (

Indexed as

Antiviral AgentsCarboxylic AcidsCyclopentanesSARS-CoV-2Viral Nonstructural ProteinsCrystallography, X-RayCysteine EndopeptidasesDrug DesignHumansModels, MolecularStructure-Activity RelationshipAntiviral AgentsCarboxylic AcidsCyclopentanesCysteine EndopeptidasesViral Nonstructural Proteins

Identifiers

PMID42439527
PMCPMC13403239

What Socratic 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 Socratic graph.