Rational prioritization strategy allows the design of macrolide derivatives that overcome antibiotic resistance.

ABSTRACT: Antibiotic resistance is a major threat to global health; this problem can be addressed by the development of new antibacterial agents to keep pace with the evolutionary adaptation of pathogens. Computational approaches are essential tools to this end since their application enables fast and early strategical decisions in the drug development process. We present a rational design approach, in which acylide antibiotics were screened based on computational predictions of solubility, membrane permeability, and binding affinity toward the ribosome. To assess our design strategy, we tested all candidates for in vitro inhibitory activity and then evaluated them in vivo with several antibiotic-resistant strains to determine minimal inhibitory concentrations. The predicted best candidate is synthe

SUBMITTER: Konig G 

PROVIDER: S-EPMC8609559 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature