Evidence map›Paper›PMID 40598773›Full record

ArticleFEBS open bio2025

NMR screening of low molecular weight inhibitors targeting the papain-like protease (PLPro) of SARS-CoV-2.

Dennis J Pyper, Sridhar Sreeramulu, Benjamin T Lanham, Elizabeth M Engle, David Fushman, Harald Schwalbe

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Article in FEBS open bio, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Dennis J PyperInstitute of Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Goethe-University Frankfurt/M, Germany.
Sridhar SreeramuluInstitute of Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Goethe-University Frankfurt/M, Germany.
Benjamin T LanhamCenter for Biomolecular Structure and Organization, Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA.
Elizabeth M EngleCenter for Biomolecular Structure and Organization, Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA.
David FushmanCenter for Biomolecular Structure and Organization, Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA.
Harald SchwalbeInstitute of Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Goethe-University Frankfurt/M, Germany.ORCID https://orcid.org/0000-0001-5693-7909

Funding

Deutsche Forschungsgemeinschaft 277478796Deutsche Forschungsgemeinschaft 277479031Deutsche Forschungsgemeinschaft 392682309Deutsche Forschungsgemeinschaft 45263286Deutsche Forschungsgemeinschaft 70653611Deutsche Forschungsgemeinschaft SCHW 701/21-1Deutsche Forschungsgemeinschaft SCHW 701/21-2European Union's Horizon 2020 research and innovation program 101094131European Union's Horizon 2020 research and innovation program 871037Hessisches Ministerium für Wissenschaft und Kunst IWB-EFRE-program 20007375Jenny T. Sih Endowed Memorial FellowshipMaryland Summer ScholarshipUniversity of Maryland
6 · The paper itself

Abstract

The Papain-like protease (PLPro) from SARS-CoV-2 plays an important role in the cleavage of the polyproteins Pp1a and Pp1ab as well as in the suppression of the immune response by deISG15ylation. Considerable effort is therefore devoted to developing low molecular weight inhibitors as starting points for antiviral drugs. Here, we present the results of an NMR screening study of PLPro for binding to the DSI-poised fragment library containing 607 compounds. Based on saturation-transfer difference (STD)- and WaterLOGSY-NMR experiments, we identified 86 binding compounds. We prioritized five candidates for further in-depth analysis. For three of those, we determined dissociation constants and two distinct binding sites on PLPro. These compounds could serve as a basis for future drug design studies in medicinal chemistry.

Indexed as

Antiviral AgentsCoronavirus 3C ProteasesCoronavirus Papain-Like ProteasesProtease InhibitorsSARS-CoV-2Binding SitesCOVID-19COVID-19 Drug TreatmentDrug Evaluation, PreclinicalHumansMagnetic Resonance SpectroscopyMolecular WeightProtein BindingAntiviral AgentsCoronavirus 3C ProteasesCoronavirus Papain-Like Proteasespapain-like protease, SARS-CoV-2Protease Inhibitorscoronavirusfragment‐based NMR screeningNMR spectroscopyNsp3dpapain‐like protease PLProSARS‐CoV‐2

Identifiers

PMID40598773
PMCPMC12485815

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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.