Approaches to the Structure-Based Design of Antivirulence Drugs: Therapeutics for the Post-Antibiotic Era

The alarming rise of multidrug-resistant bacterial strains, coupled with decades of stagnation in the field of antibiotic development, necessitates exploration of new therapeutic approaches to treat bacterial infections. Targeting bacterial virulence is an attractive alternative to traditional antibiotics in that this approach disarms pathogens that cause human diseases, without placing immediate selective pressure on the target bacterium or harming commensal species. The growing number of validated virulence protein targets for which structural information has been obtained, along with advances in computational power and screening algorithms, make the rational design of antivirulence drugs a promising avenue to explore. Here, we review the principles of structure-based drug design and the exciting opportunities this technique presents for antivirulence drug discovery.