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Natural antimicrobial peptides defend host organisms against microbes, but most have modest direct antibiotic activity. This article reviews the latest computer-assisted design strategies to develop enhanced peptide variants, and examines emerging data from clinical trials. These broad-spectrum peptides could lead to the development of next-generation antibiotics.
Interfacial inhibitors bind to the interfaces of macromolecular machines (for example, polymerases or ribosomes) and stall their progress. A number of natural product and synthetic interfacial inhibitors are in the clinic for the treatment of cancer and bacterial infections. Here, Pommier and Marchand review the concept of interfacial inhibition, and discuss the rationale and methods for the discovery of novel interfacial inhibitors.