ArticleEuropean journal of medicinal chemistry2021
Indomethacin-based PROTACs as pan-coronavirus antiviral agents.
Article in European journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 92 citations in OpenAlex.
- The potential role of indomethacin in COVID-19 management: A systematic review of therapeutic and mechanistic evidence.New microbes and new infections · 2026Review
- Ubiquitination and autophagy in host-pathogen interactions: from immune surveillance to therapeutic targeting.Nature reviews. Immunology · 2026Review
- Community-Acquired Pneumonia in Patients With Diabetes: Narrative Review.JMIR diabetes · 2026Review
- Proof of concept: targeted protein degradation of the stress granules component G3BP1 as an antiviral strategy against norovirus infection.Antimicrobial agents and chemotherapy · 2026Article
- Integrated computational screen and validation of thalidomide-based PROTACs targeting SARS-CoV-2 main protease.RSC medicinal chemistry · 2026Article
- Innovative Therapies for Oncogenic KRAS Mutations: Precision Strategies with PROTACs in Cancer Treatment.Anti-cancer agents in medicinal chemistry · 2026Review
- Evolution of proteolysis-targeting chimeras (PROTAC) technology to overcome challenges of antimicrobial resistance.npj antimicrobials and resistance · 2025Review
- PROTACs in Antivirals: Current Advancements and Future Perspectives.Molecules (Basel, Switzerland) · 2025Review
- PROTAC-Based Antivirals for Respiratory Viruses: A Novel Approach for Targeted Therapy and Vaccine Development.Microorganisms · 2025Review
- Antiviral strategies against influenza virus: an update on approved and innovative therapeutic approaches.Cellular and molecular life sciences : CMLS · 2025Review
- PROteolysis TArgeting Chimeras (PROTACs) and beyond: targeted degradation as a new path to fight microbial pathogens.FEMS microbiology reviews · 2025Review
- Targeted protein degradation: advances in drug discovery and clinical practice.Signal transduction and targeted therapy · 2024Review
- Lessons learnt from broad-spectrum coronavirus antiviral drug discovery.Expert opinion on drug discovery · 2024Review
- Review
- Targeted degrader technologies as prospective SARS-CoV-2 therapies.Drug discovery today · 2024Review
- PROTAC Beyond Cancer- Exploring the New Therapeutic Potential of Proteolysis Targeting Chimeras.Current topics in medicinal chemistry · 2024Review
- Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review.European journal of medicinal chemistry · 2023Review
- Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response.iScience · 2023Article
- Indole-Based Compounds as Potential Drug Candidates for SARS-CoV-2.Molecules (Basel, Switzerland) · 2023Review
- Antiviral PROTACs: Opportunity borne with challenge.Cell insight · 2023Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Indomethacin (INM), a well-known non-steroidal anti-inflammatory drug, has recently gained attention for its antiviral activity demonstrated in drug repurposing studies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Although the mechanism of action of INM is not yet fully understood, recent studies have indicated that it acts at an early stage of the coronaviruses (CoVs) replication cycle. In addition, a proteomic study reported that the anti-SARS-CoV-2 activity of INM could be also ascribed to its ability to inhibit human prostaglandin E synthase type 2 (PGES-2), a host protein which interacts with the SARS-CoV-2 NSP7 protein. Although INM does not potently inhibit SARS-CoV-2 replication in infected Vero E6 cells, here we have explored for the first time the application of the Proteolysis Targeting Chimeras (PROTACs) technology in order to develop more potent INM-derived PROTACs with anti-CoV activity. In this study, we report the design, synthesis, and biological evaluation of a series of INM-based PROTACs endowed with antiviral activity against a panel of human CoVs, including different SARS-CoV-2 strains. Two PROTACs showed a strong improvement in antiviral potency compared to INM. Molecular modelling studies support human PGES-2 as a potential target of INM-based antiviral PROTACs, thus paving the way toward the development of host-directed anti-CoVs strategies. To the best of our knowledge, these PROTACs represent the first-in-class INM-based PROTACs with antiviral activity and also the first example of the application of PROTACs to develop pan-coronavirus agents.
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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 Socratic graph.