A novel class of small-molecule inhibitors targeting bacteriophage infection

Abstract

Bacteriophages have emerged as important factors in human health and disease, with elevated phage levels associated with exacerbated inflammatory bowel disease, type 2 diabetes and poor outcomes in skin and lung infections. The mechanisms linking phages to these pathologies remain largely unknown, partly because specific chemical tools inhibiting bacteriophage replication (phage blockers) are lacking. Here, we identify benzimidazylpyrazoles as novel bacteriophage antivirals. Unlike existing synthetic antiphage compounds benzimidazylpyrazoles do not intercalate DNA and target an early stage of phage infection after adsorption. An optimized derivative reduced phage titer up to 10⁵-fold and demonstrated activity against different phage morphotypes and bacterial hosts, establishing it as a valuable chemical tool for the study of disease-related phage–host interactions.