ArticleNature communications2025
PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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
11 citing papers in PubMed.
- Synthesis and evaluation of 3,5-disubstituted isothiazolo[4,5-b]pyridines, pyrazolo[4,3-b]pyridines and isothiazolo[3,4-b]pyrazines as inhibitors of PIKfyve.Bioorganic chemistry · 2026Article
- Atlastin-2-mediated endoplasmic reticulum membrane tethering is critical for flavivirus replication.PLoS biology · 2026Article
- Lipid nanoparticles as active biointerfaces: From membrane interaction to systemic dysregulation.Acta pharmaceutica Sinica. B · 2026Review
- Targeting PIKfyve: Chemical Biology and Drug Discovery Insights.Chemical biology & drug design · 2026Review
- Targeting the senescence‒autophagy axis via p16Signal transduction and targeted therapy · 2026Article
- Behind the membranous curtain-lipid dynamics and functions in coronaviral replication.Journal of virology · 2026Review
- Autophagy hub genes mediate photodynamic therapy tolerance in nasopharyngeal carcinoma through cytoprotective autophagy and survival signaling.Journal of molecular histology · 2026Article
- Organoids for disease modeling and treatment: state-of-the-art.Experimental hematology & oncology · 2026Review
- Synthesis, structure-activity relationships, and SARS-CoV-2 antiviral activity of 3,5-disubstituted isothiazolo[4,3-Frontiers in chemistry · 2026Article
- Structure-Activity Relationship Study of 3-Alkynyl-6-aryl-isothiazolo[4,3-Pharmaceuticals (Basel, Switzerland) · 2025Article
- Is Autophagy a Friend or Foe in SARS-CoV-2 Infection?Viruses · 2024Review
Corrections and comments
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Authors and funding
34 authors.
Funding
Abstract
In search for broad-spectrum antivirals, we discover a small molecule inhibitor, RMC-113, that potently suppresses the replication of multiple RNA viruses including SARS-CoV-2 in human lung organoids. We demonstrate selective inhibition of the lipid kinases PIP4K2C and PIKfyve by RMC-113 and target engagement by its clickable analog. Lipidomics analysis reveals alteration of SARS-CoV-2-induced phosphoinositide signature by RMC-113 and links its antiviral effect with functional PIP4K2C and PIKfyve inhibition. We identify PIP4K2C's roles in SARS-CoV-2 entry, RNA replication, and assembly/egress, validating it as a druggable antiviral target. Integrating proteomics, single-cell transcriptomics, and functional assays, reveals that PIP4K2C binds SARS-CoV-2 nonstructural protein 6 and regulates virus-induced autophagic flux impairment. Promoting viral protein degradation by reversing autophagic flux impairment is a mechanism of antiviral action of RMC-113. These findings reveal virus-induced autophagy regulation via PIP4K2C, an understudied kinase, and propose dual PIP4K2C and PIKfyve inhibition as a candidate strategy to combat emerging viruses.
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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.