*3.5. Dengue Virus*

To date, little research has been performed to characterize the antiviral activity of LL-37 against DENV. However, a recent study demonstrated that treatment of dengue virus 2 (DENV-2) with LL-37 inhibits viral infection in green monkey kidney (Vero) cells. Incubation of virus with LL-37 (10-15 μM) prior to infection inhibits production of viral particles, whereas pre-treatment of cells with LL-37 demonstrates no effect on viral replication [43]. Molecular docking studies of DENV-2 E protein have revealed the direct binding of LL-37 with E2 protein moieties, further demonstrating the peptide's ability to act as an entry inhibitor [43]. A more recent study assessed truncated and full length variants of LL-37 against other serotypes of DENV which revealed the inhibitory properties of LL-37 required the full length peptide [55]. In comparison to DENV-2, DENV-4 required higher concentrations of LL-37 for inhibition with effect being not as potent as with the former. DENV-1 and DENV-3 inhibition however, was prominent at lower concentrations of LL-37 [55]. A recent study using DENV-2 infected keratinocytes has demonstrated the production of AMPs by infected cells as well as bystander cells [56]. Pre-incubation of cells with LL-37 prior to DENV-2 infection results in a significant decrease in viral titers and replication in infected keratinocytes, whereas HBD2 and HBD3 demonstrate minimal inhibition [56]. Additionally, as vitamin D is an inducer of LL-37 expression, supplementation of populations with vitamin D prior to DENV outbreak seasons has been suggested as a possible preventative strategy to control the virus at initial stages of infection [43].
