Comprehensive Identification and Mechanistic Evaluation of Novel DHODH Inhibitors as Potent Broad-Spectrum Antiviral Agents.

ABSTRACT: Background/Objectives: This study identifies novel dihydroorotate dehydrogenase (DHODH) inhibitors exhibiting potent broad-spectrum antiviral agents, particularly against influenza A virus (A/PR/8/34(H1N1)) and SARS-CoV-2. Methods: Structure-based virtual screening of 1.6 million compounds (ChemDiv and TargetMol databases) yielded 10 candidates, with compounds 6, 9, and 10 demonstrating significant anti-influenza activity (IC₅₀ = 4.85 ± 0.58, 7.35 ± 1.65, and 1.75 ± 0.28 μM, respectively). Building on these, molecular hybridization principles and scaffold hopping principles were applied to design and synthesize six novel compounds (11-16) through cyclization, coupling, and carboxylate deprotection. Prior to subsequent biological a

SUBMITTER: Zhang C 

PROVIDER: S-EPMC12472551 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature