ArticleBiochemical pharmacology2008
Thiopurine analogues inhibit papain-like protease of severe acute respiratory syndrome coronavirus.
Article in Biochemical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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.
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.
Who cites it
65 citing papers in PubMed, 106 citations in OpenAlex.
- Structural Basis and Inhibitor Development of SARS-CoV-2 Papain-like Protease.Molecules (Basel, Switzerland) · 2026Review
- Viral deubiquitinating proteases and the promising strategies of their inhibition.Virus research · 2024Review
- Identification of SARS-CoV-2 Main Protease Inhibitors Using Chemical Similarity Analysis Combined with Machine Learning.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Antiviral Potential of Azathioprine and Its Derivative 6- Mercaptopurine: A Narrative Literature Review.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Targeting SARS-CoV-2 nonstructural protein 3: Function, structure, inhibition, and perspective in drug discovery.Drug discovery today · 2024Review
- Identification and characterization of aurintricarboxylic acid as a potential inhibitor of SARS-CoV-2 PLpro.International journal of biological macromolecules · 2023Article
- Screening and identification of potential MERS-CoV papain-like protease (PLpro) inhibitors; Steady-state kinetic and Molecular dynamic studies.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Targeting SARS-CoV-2 papain-like protease in the postvaccine era.Trends in pharmacological sciences · 2022Review
- Chemical screen uncovers novel structural classes of inhibitors of the papain-like protease of coronaviruses.iScience · 2022Article
- The effect of various compounds on the COVID mechanisms, from chemical to molecular aspects.Biophysical chemistry · 2022Review
- Thiopurines inhibit coronavirus Spike protein processing and incorporation into progeny virions.PLoS pathogens · 2022Article
- Conserved coronavirus proteins as targets of broad-spectrum antivirals.Antiviral research · 2022Article
- Progress and Challenges in Targeting the SARS-CoV-2 Papain-like Protease.Journal of medicinal chemistry · 2022Review
- Validation and Invalidation of SARS-CoV-2 Papain-like Protease Inhibitors.ACS pharmacology & translational science · 2022Article
- Exploring naphthyl derivatives as SARS-CoV papain-like protease (PLpro) inhibitors and its implications in COVID-19 drug discovery.Molecular diversity · 2022Article
- Article
- Unmasking of crucial structural fragments for coronavirus protease inhibitors and its implications in COVID-19 drug discovery.Journal of molecular structure · 2021Article
- Binding of SARS-CoV Covalent Non-Covalent Inhibitors to the SARS-CoV-2 Papain-Like Protease and Ovarian Tumor Domain Deubiquitinases.Biomolecules · 2021Article
- Thiopurines activate an antiviral unfolded protein response that blocks influenza A virus glycoprotein accumulation.Journal of virology · 2021Article
- An update review of emerging small-molecule therapeutic options for COVID-19.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The papain-like protease of severe acute respiratory syndrome coronavirus (PLpro) (EC 3.4.22.46) is essential for the viral life cycle and therefore represents an important antiviral target. We have identified 6MP and 6TG as reversible and slow-binding inhibitors of SARS-CoV PLpro, which is the first report about small molecule reversible inhibitors of PLpro. The inhibition mechanism was investigated by kinetic measurements and computer docking. Both compounds are competitive, selective, and reversible inhibitors of the PLpro with K(is) values approximately 10 to 20 microM. A structure-function relationship study has identified the thiocarbonyl moiety of 6MP or 6TG as the active pharmacophore essential for these inhibitions, which has not been reported before. The inhibition is selective because these compounds do not exert significant inhibitory effects against other cysteine proteases, including SARS-CoV 3CLpro and several cathepsins. Thus, our results present the first potential chemical leads against SARS-CoV PLpro, which might be used as lead compounds for further optimization to enhance their potency against SARS-CoV. Both 6MP and 6TG are still used extensively in clinics, especially for children with acute lymphoblastic or myeloblastic leukemia. In light of the possible inhibition against subset of cysteine proteases, our study has emphasized the importance to study in depth these drug actions in vivo.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.