Identification of the Imidazo[1,2-a]pyrazine Derivative A4 as a Potential Influenza Virus Nucleoprotein Inhibitor.

ABSTRACT: Influenza A viruses (IAVs) have gradually developed resistance to FDA-approved drugs, which increases the need to discover novel antivirals with new mechanisms of action. Here, we used a phenotypic screening strategy and discovered that the imidazo[1,2-a]pyrazine derivative A4 demonstrates potent and broad-spectrum anti-influenza activity, especially for the oseltamivir-resistant H1N1/pdm09 strain. Indirect immunofluorescence assays revealed that A4 induces clustering of the viral nucleoprotein (NP) and prevents its nuclear accumulation. Furthermore, upon conducting binding analyses between A4 and the influenza NP using surface plasmon resonance assays and molecular docking simulations, we were able to confirm that A4 binds directly to the viral NP. Addit

SUBMITTER: Li P 

PROVIDER: S-EPMC10714431 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature