Thonningianin A disrupts pA104R-DNA binding and inhibits African swine fever virus replication.

ABSTRACT: African swine fever is a highly lethal disease caused by the African swine fever virus (ASFV), posing a significant threat to the global pig industry, wherease no approved treatments are currently available. The ASFV DNA-binding protein, pA104R, plays a critical role in viral genome packaging and replication, making it a key target for drug discovery. Through structure-based virtual screening, we identified a polyphenolic compound, thonningianin A, which disrupts the pA104R-DNA binding and significantly inhibits ASFV replication. Mechanistic study revealed that thonningianin A binds to the DNA-binding region of pA104R, forming strong hydrogen bonds with H100 and occupying the vital DNA-binding residues K92, R94, and K97. In addition, we resolved the high-resolution (1.8 Å) structure of pA1

SUBMITTER: Li QJ 

PROVIDER: S-EPMC11966994 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature