Bithiazole Inhibitors of Phosphatidylinositol 4-Kinase (PI4KIIIß) as Broad-Spectrum Antivirals Blocking the Replication of SARS-CoV-2, Zika Virus, and Human Rhinoviruses.
ChemMedChem
; 16(23): 3548-3552, 2021 12 06.
Article
in English
| MEDLINE | ID: covidwho-1400781
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 PI4KIIIß, as a promising strategy for inhibiting the replication of multiple viruses hijacking this protein. We show that bithiazole inhibitors of PI4KIIIß 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 PI4KIIIß inhibition, the role of PI4KIIIß in SARS-CoV-2 entry/replication is debated.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Rhinovirus
/
Thiazoles
/
Virus Replication
/
1-Phosphatidylinositol 4-Kinase
/
Enzyme Inhibitors
/
Zika Virus
/
SARS-CoV-2
Limits:
Humans
Language:
English
Journal:
ChemMedChem
Journal subject:
Pharmacology
/
Chemistry
Year:
2021
Document Type:
Article
Affiliation country:
Cmdc.202100483
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