Evidence map›Paper›PMID 39789725›Full record

ArticleBiochemistry2025

A High-Throughput Screening Pipeline to Identify Methyltransferase and Exonuclease Inhibitors of SARS-CoV-2 NSP14.

Quinlin Hanson, Xin Hu, Sourav Pal, Katlin Recabo, Lin Ye, Ivy Poon, John-Paul Denson, Simon Messing, Min Shen, Kelli M Wilson and 3 more

Abstract read
In one paragraph

Article in Biochemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

13 authors.

Quinlin HansonNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.ORCID 0000-0001-6033-8415
Xin HuNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
Sourav PalNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
Katlin RecaboNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
Lin YeNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
Ivy PoonProtein Expression Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, United States.
John-Paul DensonProtein Expression Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, United States.ORCID 0009-0004-1191-5641
Simon MessingProtein Expression Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, United States.
Min ShenNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.ORCID 0000-0002-8218-0433
Kelli M WilsonNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.ORCID 0000-0003-2636-2766
Alexey ZakharovNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.ORCID 0000-0003-2466-1711
Dominic EspositoProtein Expression Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, United States.
Natalia J MartinezNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
Intramural NIH HHS Z99 TR999999NCI NIH HHS 75N91019D00024
6 · The paper itself

Abstract

SARS-CoV-2 infections led to a worldwide pandemic in 2020. As of 2024, therapeutics against SARS-CoV-2 have continued to be desirable. NSP14 is a dual-function methyltransferase (MTase) and exonuclease (ExoN) with key roles in SARS-CoV-2 genome propagation and host immune system evasion. In this work, we developed high-throughput screening (HTS) assays for NSP14 MTase and ExoN activities. We screened both activities against a collection of 40,664 compounds. A total of 1677 initial hit compounds were identified, cherrypicked, counterscreened for assay interference, and screened for off-target selectivity. We identified 396 and 174 high-quality hits against the MTase and ExoN activities, respectively. Along with inhibitors for individual activities, we identified dual-activity inhibitors, including a novel inhibitor that is not competitive with any substrate and interacts with a putative allosteric binding site. This study represents the largest published screen of SARS-CoV-2 NSP14 MTase and ExoN activities to date and culminates in a pipeline for the NSP14 drug discovery.

Indexed as

Antiviral AgentsCOVID-19 Drug TreatmentEnzyme InhibitorsExonucleasesHigh-Throughput Screening AssaysMethyltransferasesSARS-CoV-2Viral Nonstructural ProteinsCOVID-19ExoribonucleasesHumansAntiviral AgentsEnzyme InhibitorsExonucleasesExoribonucleasesMethyltransferasesNSP14 protein, SARS-CoV-2Viral Nonstructural Proteins

Identifiers

PMID39789725
PMCPMC12965331

What Socratic holds

Textmetadata
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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 Socratic graph.