ABSTRACT
The Front Cover shows bithiazole derivatives acting as broad-spectrum antiviral agents (BSAAs) by targeting human host cells. These molecules block the replication of human rhinoviruses (hRVs) and Zika virus (ZIKV) via inhibition of the intracellular protein PI4KIII? while the inhibition of SARS-CoV-2 entry and replication seems to be connected with the modulation of an additional target. Cover design by Marco Radi. More information can be found in the Communication by Maria?Grazia Martina, Marco Radi et?al.
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.