Evidence map›Paper›PMID 40959264›Full record

ArticleACS medicinal chemistry letters2025

Discovery of Novel Isofunctional SARS-CoV‑2 NSP14 RNA Cap Methyltransferase Inhibitors by Structure-Based Virtual Screening.

Cindy Meyer, Mayako Michino, David J Huggins, Aitor Garzia, Jada A Davis, Michael W Miller, Nigel Liverton, Hans-Heinrich Hoffmann, J Fraser Glickman, Julius Nitsche and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS medicinal chemistry letters, 2025. 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

15 authors.

Cindy MeyerLaboratory for RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.ORCID https://orcid.org/0000-0003-3807-8383
Mayako MichinoSanders Tri-Institutional Therapeutics Discovery Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
David J HugginsSanders Tri-Institutional Therapeutics Discovery Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
Aitor GarziaLaboratory for RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
Jada A DavisLaboratory for RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
Michael W MillerSanders Tri-Institutional Therapeutics Discovery Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
Nigel LivertonSanders Tri-Institutional Therapeutics Discovery Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
Hans-Heinrich HoffmannLaboratory of Virology and Infectious Disease, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
J Fraser GlickmanFisher Drug Discovery Resource Center, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
Julius NitschePROTEROS Biostructures GmbH, Bunsenstrasse 7a, 82152 Planegg-Martinsried, Germany.
Oleg GanichkinPROTEROS Biostructures GmbH, Bunsenstrasse 7a, 82152 Planegg-Martinsried, Germany.
Stefan SteinbacherPROTEROS Biostructures GmbH, Bunsenstrasse 7a, 82152 Planegg-Martinsried, Germany.
Charles M RiceLaboratory of Virology and Infectious Disease, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
Peter T MeinkeSanders Tri-Institutional Therapeutics Discovery Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.ORCID https://orcid.org/0000-0002-7548-6215
Thomas TuschlLaboratory for RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.

Funding

Virology CoreU19AI171401 · NIAID · HACKENSACK UNIVERSITY MEDICAL CENTER · PI David S Perlin, Charles M Rice · 2022 to 2026
$92.9M
NIAID NIH HHS U19 AI171401
6 · The paper itself

Abstract

In early 2020, SARS-CoV-2 spread into a worldwide pandemic, causing more than 7 million deaths. Direct-acting antivirals (DAAs) complementing vaccines and mitigating severe disease in at-risk populations remain important. Here, we used a structure-based virtual screening (SBVS) workflow to identify new SAH-dependent inhibitors of the SARS-CoV-2 RNA cap methyltransferase NSP14. We virtually screened the Enamine and Sigma in-stock screening collections as well as the 3 orders of magnitude larger Enamine REAL make-on-demand compound library, which produced better docking scores and higher virtual hit rates. While biochemical testing of 145 in-stock library compounds yielded a single NSP14-specific inhibitor, 123 chemically synthesized Enamine REAL SBVS compounds contained 10 hits specifically inhibiting NSP14 with half-maximal inhibitory concentrations (IC

Indexed as

Coronavirusdrug developmenthigh throughput screeningNSP14RNA methyltransferasestructure-based virtual screening

Identifiers

PMID40959264
PMCPMC12434519

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.