Virtual Screening-Guided Discovery of a Selective TRPV1 Pentapeptide Inhibitor with Topical Anti-Allergic Efficacy.

ABSTRACT: Transient receptor potential vanilloid 1 (TRPV1) channels are critical mediators of cutaneous allergic inflammation, contributing to pruritus, erythema, and hypersensitivity in allergic skin disorders. Despite their therapeutic potential, clinically available TRPV1 inhibitors remain limited, leaving effective treatment options lacking. Here, we focused on a self-constructed virtual pentapeptide library and identified a highly selective TRPV1 inhibitor that demonstrated pronounced anti-allergic effects in human skin assays. Through structure-based virtual screening of approximately 200,000 peptide conformations, five candidate pentapeptides, especially P5 (DQKNC), exhibited the inhibition. Electrophysiological recordings showed that P5 inhibited TRPV1 currents with nanomolar potency, while

SUBMITTER: Liu L 

PROVIDER: S-EPMC12786063 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature