Targeting Innate Immunity for Antiviral Therapy through Small Molecule Agonists of the RLR Pathway.
Sowmya PattabhiCourtney R WilkinsRan DongMegan L KnollJeffrey PosakonyShari KaiserChad E MireMyra L WangRenee C IretonThomas W GeisbertKristin M BedardShawn P IadonatoYueh-Ming LooMichael GalePublished in: Journal of virology (2015)
Incidences of emerging and reemerging RNA viruses highlight a desperate need for broad-spectrum antiviral agents that can effectively control infections caused by viruses of distinct genera. We identified small molecule compounds that can selectively activate IRF3 for the purpose of identifying drug-like molecules that can be developed for the treatment of viral infections. Here, we report the discovery of a hydroxyquinoline family of small molecules that can activate IRF3 to promote cellular antiviral responses. These molecules can prophylactically or therapeutically control infection in cell culture by pathogenic RNA viruses, including West Nile virus, dengue virus, hepatitis C virus, influenza A virus, respiratory syncytial virus, Nipah virus, Lassa virus, and Ebola virus. Our study thus identifies a class of small molecules with a novel mechanism to enhance host immune responses for antiviral activity against a variety of RNA viruses that pose a significant health care burden and/or that are known to cause infections with high case fatality rates.
Keyphrases
- small molecule
- dengue virus
- hepatitis c virus
- healthcare
- respiratory syncytial virus
- immune response
- protein protein
- dendritic cells
- zika virus
- sars cov
- emergency department
- nucleic acid
- gene expression
- stem cells
- genetic diversity
- cancer therapy
- genome wide
- high throughput
- combination therapy
- mesenchymal stem cells
- bone marrow
- electronic health record