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Bithiazole Inhibitors of Phosphatidylinositol 4-Kinase (PI4KIIIβ) as Broad-Spectrum Antivirals Blocking the Replication of SARS-CoV-2, Zika Virus and Human Rhinoviruses
- Source :
- ChemMedChem, 16(23), 3548. John Wiley and Sons Ltd, Chemmedchem
- Publication Year :
- 2021
-
Abstract
- Over half a century since the description of the first antiviral drug, “old” re‐emerging viruses and “new” emerging viruses still represent a serious threat to global health. Their high mutation rate and rapid selection of resistance toward common antiviral drugs, together with the increasing number of co‐infections, make the war against viruses quite challenging. Herein we report a host‐targeted approach, based on the inhibition of the lipid kinase PI4KIIIβ, as a promising strategy for inhibiting the replication of multiple viruses hijacking this protein. We show that bithiazole inhibitors of PI4KIIIβ block the replication of human rhinoviruses (hRV), Zika virus (ZIKV) and SARS‐CoV‐2 at low micromolar and sub‐micromolar concentrations. However, while the anti‐hRV/ZIKV activity can be directly linked to PI4KIIIβ inhibition, the role of PI4KIIIβ in SARS‐CoV‐2 entry/replication is debated.<br />Host targeting is a promising approach for the development of broad‐spectrum antiviral agents (BSAAs) endowed with a high genetic barrier to resistance and efficacy against viral mutants resistant to conventional antiviral drugs. We show that bithiazole inhibitors of the host lipid kinase PI4KIIIβ block the replication of human rhinoviruses (hRV), Zika virus (ZIKV) and SARS‐CoV‐2 at low micromolar and sub‐micromolar concentrations. Moreover, inhibition of SARS‐CoV‐2 entry seems to be connected with an additional unknown target.
- Subjects :
- Mutation rate
viruses
medicine.disease_cause
Virus Replication
Biochemistry
Broad-spectrum antivirals
Zika virus
chemistry.chemical_compound
Pharmacology, Toxicology and Pharmaceutics(all)
Drug Stability
Drug Discovery
General Pharmacology, Toxicology and Pharmaceutics
Enzyme Inhibitors
1-Phosphatidylinositol 4-Kinase
Blocking (linguistics)
0303 health sciences
biology
Kinase
Zika Virus Infection
Communication
3. Good health
rhinovirus
Broad-spectrum antivirals, PI4KIIIb, rhinovirus, zika virus, SARS-CoV-2
Molecular Medicine
Rhinovirus
medicine.drug_class
PI4KIIIb
Antiviral Agents
Cell Line
03 medical and health sciences
Very Important Paper
Replication (statistics)
medicine
Humans
zika virus
Phosphatidylinositol
030304 developmental biology
Pharmacology
030306 microbiology
SARS-CoV-2
Organic Chemistry
COVID-19
biology.organism_classification
Virology
Communications
Thiazoles
Toxicology and Pharmaceutics(all)
chemistry
Antiviral drug
bithiazole
Subjects
Details
- Language :
- English
- ISSN :
- 18607179
- Database :
- OpenAIRE
- Journal :
- ChemMedChem, 16(23), 3548. John Wiley and Sons Ltd, Chemmedchem
- Accession number :
- edsair.doi.dedup.....5b2b2d5dd1fc50f7a61c2488ee2fca91