*3.12. Venezuelan Equine Encephalitis Virus*

Venezuelan equine encephalitis virus (VEEV) is an alphavirus that has been categorized as biothreat agent due to ease of aerosolization and high retention of infectivity in the aerosol form [68,69]. Currently there are no FDA approved therapeutics to combat VEEV infections. LL-37 has recently demonstrated anti-VEEV activity in vitro [70]. A significant decrease in intracellular VEEV genomic RNA copies was observed upon pre-incubation of LL-37 (10 μg/mL) and VEEV. Microscopy data revealed the extracellular aggregation of VEEV virions, suggesting the mechanism of action of LL-37 against VEEV is through direct interaction with viral particles, thereby inhibiting entry [70]. Pre-treatment of human microglial cells with LL-37 prior to infection also resulted in a significant reduction in VEEV titers, suggesting entry prevention is not the only mechanism of LL-37-mediated inhibition. Indeed, LL-37 increased the expression of type I interferon (IFNβ), possibly inducing an antiviral state [70]. LL-37 could prove as a potent therapeutic candidate against VEEV and possibly other alphaviruses.
