Virus-inspired designs of antimicrobial nanocapsules

Abstract

Antimicrobial resistance is becoming a serious burden for drug design. The challenges are in finding novel approaches for effectively targeting a number of different bacterial strains, and in delivering these to the site of action. We propose here a novel approach that exploits the assembly of antimicrobial peptidic units in nanocapsules that can penetrate and rupture the bacterial membrane. Additionally, the chemical versatility of the designed units can be tailored to specific targets and to the delivery of genetic material in the cell. The proposed design exploits a β-annulus (sequence ITHVGGVGGSIMAPVAVSRQLVGS) triskelion unit from the Tomato Bushy Stunt Virus, able to self assemble in solution, and functionalised with antimicrobial sequences to form dodecahedral antimicrobial nanocapsules. The stability and the activity of the antimicrobial β-annulus capsule is measured by molecular dynamics simulations in water and in the presence of model membranes. This journal is