# A novel class of small-molecule inhibitors targeting bacteriophage infection

## TL;DR

Scientists discovered a new class of molecules that can block bacteriophage infections, offering a tool to study how phages contribute to diseases.

## Contribution

The discovery of benzimidazylpyrazoles as non-DNA-intercalating bacteriophage antivirals targeting an early infection stage.

## Key findings

- Benzimidazylpyrazoles inhibit phage replication without DNA intercalation.
- An optimized derivative reduced phage titer up to 105-fold across multiple phage types and bacterial hosts.

## 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.

Discovery of benzimidazylpyrazoles as a new class of synthetic bacteriophage antivirals provides a chemical tool enabling the study of disease-related phage–host interactions.