| Title | Bithiazole Inhibitors of Phosphatidylinositol 4-Kinase (PI4KIIIbeta) as Broad-Spectrum Antivirals Blocking the Replication of SARS-CoV-2, Zika Virus, and Human Rhinoviruses. | ||
| 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 | ||
| Journal | ChemMedChem | Publication Year/Month | 2021-Dec |
| PMID | 34382337 | PMCID | PMC8427023 |
| Affiliation + expend | 1.Dipartimento di Scienze degli Alimenti e del Farmaco, Universita degli Studi di Parma, Parco Area delle Scienze, 27/A, 43124, Parma, Italy. | ||
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 PI4KIIIbeta, as a promising strategy for inhibiting the replication of multiple viruses hijacking this protein. We show that bithiazole inhibitors of PI4KIIIbeta 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 PI4KIIIbeta inhibition, the role of PI4KIIIbeta in SARS-CoV-2 entry/replication is debated.