SELF-ASSEMBLY INTO ROD-LIKE STRUCTURES AND ANTIMICROBIAL ACTIVITY OF A SHORT PEPTIDE DERIVED FROM THE EBOLA VIRUS GLYCOPROTEIN

Peptides derived from viral fusion proteins are excellent models for investigating structural transitions and disruption mechanisms in biological membranes. With this context in mind, we have implemented a selection protocol using computational tools based on MLCPP 2.0 and AlphaFold2 to scan the primary amino acid sequence of the glycoprotein precursor of the Ebola virus (Genbank code #QNL26815.1) to identify peptides that simultaneously exhibit membranotropic abilities and alpha-helix propensity. Among potential sequences, the hexadecapeptide WAF (WAFWETKKNLTRKIRS) stood out due to its sequential complexity and high propensity for spontaneous self-organization. With a Critical Aggregation Concentration (CAC) of ~120 µM, WAF was experimentally shown to display a striking tendency toward helical conformations, a behavior enhanced at hydrophobic interfaces. This structural transition is accompanied by a kinetic profile in Thioflavin T assays, presenting an absence of a lag phase and immediate fibrillization upon reaching the critical threshold. The rapid formation of these supramolecular networks is macroscopically evidenced by a slight increase in solution viscosity and results in the organization of nanostructures with rod-like morphology detected by AFM. The functionality of this organized helical arrangement was validated in short-term bacterial killing assays, in which WAF demonstrated effective antimicrobial activity against strains of S. aureus and E. coli at concentrations near to 250 µM. The set of data suggests that the membranotropic activity of WAF is governed by its folding into amphipathic helices and its capacity to establish ordered nanostructures that promote membrane lysis, consolidating it as a potential prototype for the development of new therapeutic agents.