Bithiazole Inhibitors of Phosphatidylinositol 4-Kinase (PI4KIII beta) as Broad-Spectrum Antivirals Blocking the Replication of SARS-CoV-2, Zika Virus, and Human Rhinoviruses

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 PI4KIII beta, as a promising strategy for inhibiting the replication of multiple viruses hijacking this protein. We show that bithiazole inhibitors of PI4KIII beta 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 PI4KIII beta inhibition, the role of PI4KIII beta in SARS-CoV-2 entry/replication is debated.

Automated summary

Over half a century after the first antiviral drug was described, old and new viruses still pose a serious threat to global health due to their high mutation rate and rapid resistance to common antiviral drugs. Targeting the lipid kinase PI4KIII beta could be a promising strategy for inhibiting the replication of multiple viruses, although its role in SARS-CoV-2 entry/replication is still debated.