ArticleNature communications2022
An anti-influenza A virus microbial metabolite acts by degrading viral endonuclease PA.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
- Divergent pathogenic mechanisms of influenza A and influenza B viruses.Archives of microbiology · 2026Review
- Quercetin, a flavonoid, suppresses viral proliferation by interfering with the ubiquitin transfer from E1 to E2 enzymes.PLoS pathogens · 2026Article
- Untapped microbial factories for next-generation therapeutics: Endophytic fungi of medicinal plants.Microbial cell factories · 2026Review
- Ubiquitination and autophagy in host-pathogen interactions: from immune surveillance to therapeutic targeting.Nature reviews. Immunology · 2026Review
- Anti-influenza drugs targeting trimeric RNA polymerase complex: From development to clinics.Acta pharmaceutica Sinica. B · 2026Review
- Molecular mechanism of resistance to lonafarnib conferred by mutations in the cysteine-rich region of respiratory syncytial virus fusion glycoprotein and discovery of a lonafarnib-derived antiviral PROTAC.Journal of virology · 2026Article
- Orchestrating immunopathology: the spectrum of programmed cell death pathways co-opted by influenza a virus in pulmonary immunity.Frontiers in immunology · 2026Review
- Evolution of proteolysis-targeting chimeras (PROTAC) technology to overcome challenges of antimicrobial resistance.npj antimicrobials and resistance · 2025Review
- Innovative Strategies for the Targeted Degradation of Viral Proteins: Paving the Way for Next-Generation Therapeutics.Pharmaceutics · 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
- IncRNA IPAN antagonizes RIG-I/TRIM25-mediated degradation of influenza A virus PB1 to promote viral replication.Biosafety and health · 2025Article
- Review
- A First-in-Class Dual Degrader of Bcl-2/Bcl-xL Reverses HIV Latency and Minimizes Ex Vivo Reservoirs from Patients.International journal of molecular sciences · 2025Article
- 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
- Discovery of Potent Degraders of the Dengue Virus Envelope Protein.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Targeted protein degradation: from mechanisms to clinic.Nature reviews. Molecular cell biology · 2024Review
- Broad-spectrum activity against mosquito-borne flaviviruses achieved by a targeted protein degradation mechanism.Nature communications · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emergence of new highly pathogenic and drug-resistant influenza strains urges the development of novel therapeutics for influenza A virus (IAV). Here, we report the discovery of an anti-IAV microbial metabolite called APL-16-5 that was originally isolated from the plant endophytic fungus Aspergillus sp. CPCC 400735. APL-16-5 binds to both the E3 ligase TRIM25 and IAV polymerase subunit PA, leading to TRIM25 ubiquitination of PA and subsequent degradation of PA in the proteasome. This mode of action conforms to that of a proteolysis targeting chimera which employs the cellular ubiquitin-proteasome machinery to chemically induce the degradation of target proteins. Importantly, APL-16-5 potently inhibits IAV and protects mice from lethal IAV infection. Therefore, we have identified a natural microbial metabolite with potent in vivo anti-IAV activity and the potential of becoming a new IAV therapeutic. The antiviral mechanism of APL-16-5 opens the possibility of improving its anti-IAV potency and specificity by adjusting its affinity for TRIM25 and viral PA protein through medicinal chemistry.
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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.