ArticleiScience2021
6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro.
Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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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.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- Temporal transcriptomics identifies early-response and infection-condition-specific modules guiding host-directed anti-EBOV therapeutics.Microbiology spectrum · 2026Article
- Investigating the evolutionary history of the biosynthetic gene cluster for the cytotoxic purine analog, 6-thioguanine.Molecular genetics and genomics : MGG · 2026Article
- Structural Basis and Inhibitor Development of SARS-CoV-2 Papain-like Protease.Molecules (Basel, Switzerland) · 2026Review
- The mechanism of thioamide formation by the YcfA-YcfC system in 6-thioguanine biosynthesis.Nature communications · 2025Article
- PLpro Inhibitors as a Potential Treatment for COVID-19.Biomedicines · 2025Article
- Development of a Fluorescence Polarization Assay for the SARS-CoV-2 Papain-like Protease.ACS pharmacology & translational science · 2025Article
- 6-thioguanine inhibits EV71 replication by reducing BIRC3-mediated autophagy.BMC microbiology · 2025Article
- In-cell bioluminescence resonance energy transfer (BRET)-based assay uncovers ceritinib and CA-074 as SARS-CoV-2 papain-like protease inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Native Mass Spectrometry Reveals Binding Interactions of SARS-CoV-2 PLpro with Inhibitors and Cellular Targets.ACS infectious diseases · 2024Article
- COVID-19 drug discovery and treatment options.Nature reviews. Microbiology · 2024Review
- After the Hurricane: Anti-COVID-19 Drugs Development, Molecular Mechanisms of Action and Future Perspectives.International journal of molecular sciences · 2024Review
- Targeting SARS-CoV-2 nonstructural protein 3: Function, structure, inhibition, and perspective in drug discovery.Drug discovery today · 2024Review
- Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2.RSC advances · 2023Review
- Complement factor D targeting protects endotheliopathy in organoid and monkey models of COVID-19.Cell stem cell · 2023Article
- Immunosuppressants exert differential effects on pan-coronavirus infection and distinct combinatory antiviral activity with molnupiravir and nirmatrelvir.United European gastroenterology journal · 2023Article
- Identification and characterization of aurintricarboxylic acid as a potential inhibitor of SARS-CoV-2 PLpro.International journal of biological macromolecules · 2023Article
- Role of E3 ubiquitin ligases and deubiquitinating enzymes in SARS-CoV-2 infection.Frontiers in cellular and infection microbiology · 2023Review
- A hypothesis on designing strategy of effective RdRp inhibitors for the treatment of SARS-CoV-2.3 Biotech · 2023Review
- Antiviral Disaccharide Lead Compounds against SARS-CoV-2 through Computer-Aided High-Throughput Screen.Chembiochem : a European journal of chemical biology · 2022Article
- Thiopurines inhibit coronavirus Spike protein processing and incorporation into progeny virions.PLoS pathogens · 2022Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The emergence of SARS-CoV-2 has led to a global health crisis that, in addition to vaccines and immunomodulatory therapies, calls for the identification of antiviral therapeutics. The papain-like protease (PLpro) activity of nsp3 is an attractive drug target as it is essential for viral polyprotein cleavage and for deconjugation of ISG15, an antiviral ubiquitin-like protein. We show here that 6-Thioguanine (6-TG), an orally available and widely available generic drug, inhibits SARS-CoV-2 replication in Vero-E6 cells with an EC50 of approximately 2 μM. 6-TG also inhibited PLpro-catalyzed polyprotein cleavage and de-ISGylation in cells and inhibited proteolytic activity of the purified PLpro domain
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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.