Thonningianin A disrupts pA104R−DNA binding and inhibits African swine fever virus replication
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 re...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2025.2482697 |
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| Summary: | 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. |
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| ISSN: | 2222-1751 |