Discovery of natural CdnP inhibitors through structure-based virtual screening and molecular dynamics simulations.

ABSTRACT: Tuberculosis, caused by Mycobacterium tuberculosis, remains one of the most lethal infectious diseases both historically and in the post-coronavirus disease 2019 era. CdnP (Rv2837c) functions as a bifunctional oligoribonuclease and 3'(2')-phosphoadenosine 5'-phosphate-phosphatase that impedes host immune responses by recognizing bacterial cyclic dinucleotides such as c-di-AMP, which serve as pathogen-associated molecular patterns. Despite its significance, strategies targeting CdnP remain limited. Through high-throughput virtual screening and enzymatic assays, we identified four natural product inhibitors: one coumarin derivative (macrosporusone A) and three flavonoid glucosides (ligustroflavone, rhoifolin, and neodiosmin). Surface plasmon resonance measurements confirmed direct bin

SUBMITTER: Gu X 

PROVIDER: S-EPMC12131788 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature