Search Results (2)

Flaviviruses, including West Nile virus, Zika virus, and Dengue virus, pose global health challenges due to their distribution, pathogenicity, and lack of effective treatments or vaccines. This study investigated the antiviral activity of novel truncated peptides derived from the two-peptide plantaricins PLNC8 αβ, PlnEF, PlnJK, and PlnA. The antiviral potential was predicted using machine learning tools, followed by in vitro evaluation against the Kunjin virus using plaque reduction assays in Vero cells. Molecular docking assessed peptide interactions with KUNV and ZIKV. Full-length and truncated peptides from PlnA, PlnE, PlnF, PlnJ, and PlnK demonstrated limited antiviral efficacy against KUNV in vitro, despite in silico predictions suggesting antiviral potential for PlnA, PlnE, and PlnJ. Large discrepancies were observed between the predicted and experimentally determined activities. However, complementary two-peptide plantaricins PlnEF and PlnJK exhibited significant synergistic effects. Furthermore, the truncated peptides PLNC8 α1-15 and PLNC8 β1-20 reduced KUNV viral load by over 90%, outperforming their full-length counterparts. Molecular docking revealed interactions of PLNC8 α and PLNC8 β, and their truncated variants, with KUNV and ZIKV, suggesting a mechanism involving viral envelope disruption. These findings highlight the potential of plantaricin-derived peptides as promising antiviral candidates against flaviviruses, warranting further investigation into their mechanisms and applications. Full article

PLNC8 αβ is a cationic antimicrobial peptide that previously has been reported to express both antibacterial and antiviral properties. This study aimed to further elucidate the antiviral effects of PLNC8 αβ and its impact on virus-induced cytotoxicity and inflammatory signaling in human alveolar epithelial cells (A549) infected with the flavivirus Kunjin. Complementary in silico analyses using molecular dynamics (MD) simulation were conducted to investigate the mechanism of action of PLNC8 αβ by studying the interaction of PLNC8 α and β with models of a flavivirus membrane and a eukaryotic plasma membrane, respectively. Our findings demonstrated that PLNC8 αβ significantly reduces both extracellular and intracellular viral loads, as confirmed by plaque reduction assays and RT-PCR. The peptide also mitigated virus-induced cytotoxicity and inflammation. Notably, PLNC8 αβ modulated the virus-induced dysregulation of key signaling and inflammatory genes, such as TLR9, TLR3, NOD2, FOS, JUN, IL6, and CXCL8. MD simulation revealed that PLNC8 αβ exhibits higher binding affinity for a flavivirus membrane model compared to a model of the plasma membrane, likely due to stronger electrostatic interactions with anionic phospholipids. This selective interaction possibly accounts for a potent antiviral activity of PLNC8 αβ combined with a minimal cytotoxicity toward human cells. Overall, PLNC8 αβ shows significant promise as an antiviral agent against flavivirus infections and warrants further exploration for peptide-based antiviral therapies. Full article