ArticleAntimicrobial agents and chemotherapy2013
Phosphatidylinositol 4-kinase III beta is essential for replication of human rhinovirus and its inhibition causes a lethal phenotype in vivo.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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
48 citing papers in PubMed, 82 citations in OpenAlex.
- Towards broader-spectrum direct-acting antivirals against RNA viruses.Nature reviews. Microbiology · 2026Review
- Broad-spectrum host-targeting antivirals for rhinovirus infections: mechanisms and future perspectives.Frontiers in immunology · 2026Review
- Phosphatidylinositol 4-phosphate; A minor lipid with multiple personalities.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Inositol metabolism as a broad-spectrum antiviral target.Frontiers in microbiology · 2025Review
- Identification of epidermal growth factor receptor-tyrosine kinase inhibitor targeting the VP1 pocket of human rhinovirus.Antimicrobial agents and chemotherapy · 2024Article
- Impact of the COVID-19 pandemic on severe non-SARS-CoV-2 community-acquired pneumonia in Reunion Island: a multicenter retrospective observational study, 2016-2021.Scientific reports · 2023Observational
- Vemurafenib Inhibits Acute and Chronic Enterovirus Infection by Affecting Cellular Kinase Phosphatidylinositol 4-Kinase Type IIIβ.Microbiology spectrum · 2023Article
- A Plethora of Functions Condensed into Tiny Phospholipids: The Story of PI4P and PI(4,5)PCells · 2023Review
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- Article
- Targeting Human Proteins for Antiviral Drug Discovery and Repurposing Efforts: A Focus on Protein Kinases.Viruses · 2023Review
- A Proximity biotinylation assay with a host protein bait reveals multiple factors modulating enterovirus replication.PLoS pathogens · 2022Article
- Structure-function analysis of enterovirus protease 2A in complex with its essential host factor SETD3.Nature communications · 2022Article
- Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization.Science advances · 2022Article
- Article
- Novel capsid binder and PI4KIIIbeta inhibitors for EV-A71 replication inhibition.Scientific reports · 2021Article
- Picornaviruses: A View from 3A.Viruses · 2021Review
- Review
- Experimental Antiviral Therapeutic Studies for Human Rhinovirus Infections.Journal of experimental pharmacology · 2021Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human rhinovirus (HRV) is the predominant cause of the common cold, but more importantly, infection may have serious repercussions in asthmatics and chronic obstructive pulmonary disorder (COPD) patients. A cell-based antiviral screen against HRV was performed with a subset of our proprietary compound collection, and an aminothiazole series with pan-HRV species and enteroviral activity was identified. The series was found to act at the level of replication in the HRV infectious cycle. In vitro selection and sequencing of aminothiazole series-resistant HRV variants revealed a single-nucleotide mutation leading to the amino acid change I42V in the essential HRV 3A protein. This same mutation has been previously implicated in resistance to enviroxime, a former clinical-stage antipicornavirus agent. Enviroxime-like compounds have recently been shown to target the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIIIβ). A good correlation between PI4KIIIβ activity and HRV antiviral potency was found when analyzing the data over 80 compounds of the aminothiazole series, covering a 750-fold potency range. The mechanism of action through PI4KIIIβ inhibition was further demonstrated by small interfering RNA (siRNA) knockdown of PI4KB, which reduced HRV replication and also increased the potency of the PI4KIIIβ inhibitors. Inhibitors from two different structural classes with promising pharmacokinetic profiles and with very good selectivity for PI4KIIIβ were used to dissociate compound-related toxicity from target-related toxicity. Mortality was seen in all dosing groups of mice treated with either compound, therefore suggesting that short-term inhibition of PI4KIIIβ is deleterious.
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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.