Characterisation of ten NS2B-NS3 proteases: Paving the way for pan-flavivirus drugs.

Flaviviruses can cause severe illness in humans. Effective and safe vaccines are available for some species; however, for many flaviviruses disease prevention or specific treatments remain unavailable. The viral replication cycle depends on the proteolytic activity of the NS2B-NS3 protease, which releases functional viral proteins from a non-functional polyprotein precursor, rendering the protease a promising drug target.

Cell-Penetrating Peptide-Bismuth Bicycles.

Cell-penetrating peptides (CPPs) play a significant role in the delivery of cargos into human cells. We report the first CPPs based on peptide-bismuth bicycles, which can be readily obtained from commercially available peptide precursors, making them accessible for a wide range of applications. These CPPs enter human cells as demonstrated by live-cell confocal microscopy using fluorescently labelled peptides.

Exploring biocompatible chemistry to create stapled and photoswitchable variants of the antimicrobial peptide aurein 1.2.

Antibiotic resistance is an escalating global health threat. Due to their diverse mechanisms of action and evasion of traditional resistance mechanisms, peptides hold promise as future antibiotics. Their ability to disrupt bacterial membranes presents a potential strategy to combat drug-resistant infections and address the increasing need for effective antimicrobial treatments.

Peptide-Bismuth Bicycles: In Situ Access to Stable Constrained Peptides with Superior Bioactivity.

Constrained peptides are promising next-generation therapeutics. We report here a fundamentally new strategy for the facile generation of bicyclic peptides using linear precursor peptides with three cysteine residues and a non-toxic trivalent bismuth(III) salt. Peptide-bismuth bicycles form instantaneously at physiological pH, are stable in aqueous solution for many weeks, and much more resistant to proteolysis than their linear precursors.

Targeting the protease of West Nile virus.

West Nile virus infections can cause severe neurological symptoms. During the last 25 years, cases have been reported in Asia, North America, Africa, Europe and Australia (Kunjin). No West Nile virus vaccines or specific antiviral therapies are available to date.

Inhibitors of the Zika virus protease NS2B-NS3.

In recent years, the Zika virus has emerged from a neglected flavivirus to a health-threatening pathogen that causes epidemic outbreaks associated with neurological disorders and congenital malformations. In addition to vaccine development, the discovery of specific antiviral agents has been pursued intensely. The Zika virus protease NS2B-NS3 catalyses the processing of the viral precursor polyprotein as an essential step during viral replication.