Author: Grazia Martina, Maria; Vicenti, Ilaria; Bauer, Lisa; Crespan, Emmanuele; Rango, Enrico; Boccuto, Adele; Olivieri, Noemi; Incerti, Matteo; Zwaagstra, Marleen; Allodi, Marika; Bertoni, Simona; Dreassi, Elena; Zazzi, Maurizio; van Kuppeveld, Frank J. M.; Maga, Giovanni; Radi, Marco
Title: Bithiazole Inhibitors of Phosphatidylinositol 4â€Kinase (PI4KIIIβ) as Broadâ€Spectrum Antivirals Blocking the Replication of SARSâ€CoVâ€2, Zika Virus, and Human Rhinoviruses Cord-id: j11i1yzl Document date: 2021_9_7
ID: j11i1yzl
Snippet: Over half a century since the description of the first antiviral drug, “old†reâ€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 coâ€infections, make the war against viruses quite challenging. Herein we report a hostâ€targeted approach, based on the inhibition of the lipid kinase PI4KIIIβ, as a promising strate
Document: Over half a century since the description of the first antiviral drug, “old†reâ€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 coâ€infections, make the war against viruses quite challenging. Herein we report a hostâ€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 SARSâ€CoVâ€2 at low micromolar and subâ€micromolar concentrations. However, while the antiâ€hRV/ZIKV activity can be directly linked to PI4KIIIβ inhibition, the role of PI4KIIIβ in SARSâ€CoVâ€2 entry/replication is debated.
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