Evidence map›Paper›PMID 36764586›Full record

ArticleBiochimica et biophysica acta. General subjects2023

SS148 and WZ16 inhibit the activities of nsp10-nsp16 complexes from all seven human pathogenic coronaviruses.

Fengling Li, Pegah Ghiabi, Taraneh Hajian, Martin Klima, Alice Shi Ming Li, Aliakbar Khalili Yazdi, Irene Chau, Peter Loppnau, Maria Kutera, Almagul Seitova and 5 more

Abstract read
In one paragraph

Article in Biochimica et biophysica acta. General subjects, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Review
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  5. Review
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  7. RSC medicinal chemistry · 2024
    Article
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  9. Review
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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

15 authors.

Fengling LiStructural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Pegah GhiabiStructural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Taraneh HajianStructural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada; Drug Discovery Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
Martin KlimaInstitute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague 6, Czech Republic.
Alice Shi Ming LiDrug Discovery Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Aliakbar Khalili YazdiStructural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Irene ChauStructural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Peter LoppnauStructural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Maria KuteraStructural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Almagul SeitovaStructural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Albina BolotokovaStructural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Ashley HutchinsonStructural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Sumera PerveenStructural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Evzen BouraInstitute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague 6, Czech Republic.
Masoud VedadiStructural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada; Drug Discovery Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA. Electronic address: m.vedadi@utoronto.ca.

Funding

Targeting Viroporins and Coronavirus M ProteinU19AI171110 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2022 to 2026
$103.4M
NIAID NIH HHS U19 AI171110
6 · The paper itself

Abstract

Seven coronaviruses have infected humans (HCoVs) to-date. SARS-CoV-2 caused the current COVID-19 pandemic with the well-known high mortality and severe socioeconomic consequences. MERS-CoV and SARS-CoV caused epidemic of MERS and SARS, respectively, with severe respiratory symptoms and significant fatality. However, HCoV-229E, HCoV-NL63, HCoV-HKU1, and HCoV-OC43 cause respiratory illnesses with less severe symptoms in most cases. All coronaviruses use RNA capping to evade the immune systems of humans. Two viral methyltransferases, nsp14 and nsp16, play key roles in RNA capping and are considered valuable targets for development of anti-coronavirus therapeutics. But little is known about the kinetics of nsp10-nsp16 methyltransferase activities of most HCoVs, and reliable assays for screening are not available. Here, we report the expression, purification, and kinetic characterization of nsp10-nsp16 complexes from six HCoVs in parallel with previously characterized SARS-CoV-2. Probing the active sites of all seven by SS148 and WZ16, the two recently reported dual nsp14 / nsp10-nsp16 inhibitors, revealed pan-inhibition. Overall, our study show feasibility of developing broad-spectrum dual nsp14 / nsp10-nsp16-inhibitor therapeutics.

Indexed as

COVID-19HumansMethyltransferasesPandemicsPurinesPyrimidinesPyrrolesRNASARS-CoV-2Viral Nonstructural ProteinsMethyltransferasesNSP16 protein, SARS-CoV-2ORF1ab polyprotein, SARS-CoV-2PurinesPyrimidinesPyrrolesRNASS148Viral Nonstructural ProteinsWZ16CoronavirusEnzyme kineticsEnzyme purificationnsp10-nsp16 complexRNA methyltransferaseRNA virusViral protein

Identifiers

PMID36764586
PMCPMC9908617

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.