Highly potent and selective phosphatidylinositol 4-kinase IIIβ inhibitors as broad-spectrum anti-rhinoviral agents.

ABSTRACT: Human rhinoviruses (hRVs) cause upper and lower respiratory tract infections and exacerbate asthma and chronic obstructive pulmonary disease. hRVs comprise more than 160 strains with considerable genetic variation. Their high diversity and strain-specific interactions with antisera hinder the development of anti-hRV therapeutic agents. Phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) is a key enzyme in the phosphoinositide signalling pathway that is crucial for the replication and survival of various viruses. We identified novel PI4KIIIβ inhibitors, N-(4-methyl-5-arylthiazol)-2-amide derivatives, by generating a hit compound, 1a, from the high-throughput screening of a chemical library, followed by the optimization study of 1a. Inhibitor 7e exhibited the highest activity (EC₅₀

SUBMITTER: G Vishakantegowda A 

PROVIDER: S-EPMC10880896 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature