2. Academic Validation
  3. Rapid discovery of pseudorabies virus inhibitors repurposed from the antimicrobial agent ciprofloxacin

Rapid discovery of pseudorabies virus inhibitors repurposed from the antimicrobial agent ciprofloxacin

  • Eur J Med Chem. 2025 May 5:289:117490. doi: 10.1016/j.ejmech.2025.117490.
Lin Wei 1,  Yun You 2,  Yang Hu 2,  Keke Wang 2,  Honghe Zhao 2,  Yang Cheng 2,  Junfei Zhu 2,  Jun Weng 3,  Yanliang Ren 4,  Yuhua Chen 2,  Meiting Chen 2,  Xiujuan Chen 2,  Banbin Xing 2,  Licheng Bai 2,  Han Li 2,  Peng Chen 2,  Zigong Wei 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, PR China; Hubei Jiangxia Laboratory, Wuhan, Hubei, PR China.
  • 2 State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, PR China.
  • 3 State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, PR China; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, PR China.
  • 4 Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, 430079, PR China.
  • 5 State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, PR China; Hubei Jiangxia Laboratory, Wuhan, Hubei, PR China; Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, School of life sciences, Hubei University, Wuhan, Hubei, PR China. Electronic address: weizigong@163.com.
PMID: 40085975 DOI: 10.1016/j.ejmech.2025.117490
Abstract

Pseudorabies virus (PRV) is a significant pathogen impacting swine health and poses high zoonotic risks to humans. Effective Antiviral treatments for PRV remain limited, underscoring the need for novel therapeutic strategies. In this study, ciprofloxacin was identified as a repurposed promising candidate with significant in vitro inhibition of PRV replication based on our inference from PNU-183792, an HSV-1 DNA Polymerase inhibitor, that quinolones have the potential to act as anti-PRV drugs. Compound A1 was firstly hopping from ciprofloxacin and PNU-183792, showing more than 500-fold higher anti-PRV activity than ciprofloxacin with an EC50 of 2.21 nM. Then, C2 was obtained from rapid optimization of replacing the benzyl and cyclopropyl groups of A1, which showed excellent inhibition of PRV replication with an EC50 of 0.29 nM and MIC80 in range of 1.6-8 nM. Pharmacokinetic studies demonstrated favorable properties for C2, with good plasma exposure following intraperitoneal administration. In vivo studies in Kunming mice showed that C2 inhibited PRV replication by up to 99 %. These results suggest that quinolone-based inhibitors, particularly C2, represent a viable therapeutic approach for the treatment of PRV infections and warrant further preclinical development.

Keywords

Antivirus; Ciprofloxacin; DNA polymerase; Herpesviridae family; Pseudorabies virus (PRV); Structure-based drug design (SBDD); Zoonotic.

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