BDGR-49 protects BALB/c mice from lethal, intranasal challenge of Venezuelan Equine Encephalitis Virus

Venezuelan, Western and Eastern Equine Encephalitis Virus (VEEV, WEEV and EEEV), genus Alphavirus, causes a febrile illness that may result in fatal neurological disease which has no FDA-approved antivirals for the prevention or treatment. To address this gap, we developed a novel brain-penetrant, small molecule, BDGR-49, which when administered subcutaneously at 6 mg/kg twice per day for 6 days conferred 100% protection against a lethal intranasal challenge of VEEV Trinidad donkey (TrD) in BALB/c mouse model. By eight days post-infection (dpi), viral load in the brain of BDGR-49-treated mice was significantly reduced whereas TrD-infected, sham-treated mice succumbed to disease on 5 dpi. Analysis of the host responses in the brains of VEEV TrD-infected, BDGR-49-treated, mice resulted in a significant reduction in expression of genes in pathways associated with inflammation and cell death. BALB/c mice were intranasally infected Venezuelan equine encephalitis virus (VEEV), prophylactically treated with BDGR-49 or sham-treated. At 2, 4, 5 (Sham-treated), and 8 (BDGR-49-treated) days post-infection mice were euthanized and brains collected and RNA-Seq performed on.