The D-enantiomer of LL-37 shows comparable antiviral activity against Zika virus as the native form of LL-37 a) Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Cibinong Science Center, Cibinong, Kabupaten Bogor 16911, Indonesia. Abstract Zika virus (ZIKV) is a mosquito-borne flavivirus that is predominantly transmitted by Aedes mosquitoes. ZIKV can also be transmitted vertically from mother to fetus and by sexual transmission. There is currently no effective treatment for ZIKV infections, and given the spread of this disease worldwide, there is an urgent need for new, low-cost and efficacious treatments. LL-37, the sole human cathelicidin which are part of the innate immune system, has been shown to have antiviral activity against a wide range of enveloped viral pathogens. However, a major translational limitation of LL-37 is its susceptibility to post-translational modifications (PTMs) including proteolysis. In the present study, we investigated the in-vitro effect of the native form, D-form and scrambled LL-37 on ZIKV infection in A549 cells. The intracellular viral protein was quantified using the In-Cell Western assay. The culture supernatant was assessed for infectious viral particles by plaque forming unit assay and the level of cytokine release was determined using fluorescent microbead immunoassay. The L- and D-form of LL-37 effectively reduce ZIKV infectivity in A549 cells as compared to virus control. In terms of production of viral particles, the addition of D-LL-37 post infection showed infectivity reduction with a better significance than the native LL-37. Treatment of the ZIKV with scrambled LL-37 had no effect on ZIKV infectivity and the viral load as compared to virus control. Molecular docking studies revealed possible binding of L-form and D-form of LL-37 to the ZIKV envelope (E) protein dimer. The D-form of LL-37 binds to ZIKV E protein with a better stability compared to the native form. Together, our in-vitro experiments and in-silico analyses suggest that the native and D-form of LL-37 prevent the entry of ZIKV into the cells by binding to the E protein and engineering LL-37 into more biologically stable forms improve its antiviral potential against ZIKV infections. Keywords: ZIKV, antiviral, LL-37 Topic: Biokimia Medis |
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