9JS5

Crystal structure of the ASFV-derived histone-like protein pA104R

Summary for 9JS5

• Entry DOI: 10.2210/pdb9js5/pdb
• Descriptor: Viral histone-like protein, 1,2-ETHANEDIOL, SULFATE ION, ... (4 entities in total)
• Functional Keywords: asfv, pa104r, dna binding protein
• Biological source: African swine fever virus
• Total number of polymer chains: 2
• Total formula weight: 23962.02

Authors

Li, Q.,Shao, H.,Yi, D.,Cen, S. (deposition date: 2024-09-30, release date: 2025-04-30)

Primary citation

Li, Q.J.,Shao, H.H.,Zheng, L.L.,Liu, Q.,Huo, C.C.,Yi, D.R.,Feng, T.,Cen, S.
Thonningianin A disrupts pA104R-DNA binding and inhibits African swine fever virus replication.
Emerg Microbes Infect, 14:2482697-2482697, 2025

PubMed 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 pA104R (PDB ID 9JS5), providing valuable insights for future drug screening. Together, these results demonstrate that thonningianin A holds great potential for the development of anti-ASFV drug, as a herb extract with favourable pharmacokinetic properties and safety.

PubMed: 40138179
DOI: 10.1080/22221751.2025.2482697

Experimental method

X-RAY DIFFRACTION (1.8 Å)