Virus-inspired designs of antimicrobial nanocapsules

TY - JOUR

T1 - Virus-inspired designs of antimicrobial nanocapsules

AU - Cruz, Carlos H.B.

AU - Marzuoli, Irene

AU - Fraternali, Franca

N1 - Funding Information: IM and FF acknowledge funding by the Engineering and Physical Sciences Research Council (EPSRC) through the Centre for Doctoral Training ~ Cross Disciplinary Approaches to Non-Equilibrium Systems ~ (CANES, Grant No. EP/ L015854/1). CHBC acknowledges funding from CAPES – Proc. no. 88881.197985/2018-01. This project made use of the following resources: computer time on ARCHER granted via the UK High-End Computing Consortium for Biomolecular Simulation, HECBioSim (http://www.hecbiosim.ac.uk), supported by EPSRC (grant no. EP/R029407/1); resources provided by the Cambridge Service for Data Driven Discovery (CSD3) operated by the University of Cambridge Research Computing Service (http://www.csd3.cam.ac.uk/), provided by Dell EMC and Intel using Tier-2 funding from the Engineering and Physical Sciences Research Council (capital grant EP/P020259/1), and DiRAC funding from the Science and Technology Facilities Council (https://www.dirac.ac.uk). Publisher Copyright: © The Royal Society of Chemistry.

PY - 2021

Y1 - 2021

N2 - 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

AB - 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

UR - http://www.scopus.com/inward/record.url?scp=85122357743&partnerID=8YFLogxK

U2 - 10.1039/d1fd00041a

DO - 10.1039/d1fd00041a

M3 - Article

AN - SCOPUS:85122357743

SN - 1359-6640

VL - 232

SP - 448

EP - 462

JO - Faraday Discussions

JF - Faraday Discussions

ER -