2. Academic Validation
  3. Identification of novel broad-spectrum antiviral drugs targeting the N-terminal domain of the FIPV nucleocapsid protein

Identification of novel broad-spectrum antiviral drugs targeting the N-terminal domain of the FIPV nucleocapsid protein

  • Int J Biol Macromol. 2024 Sep 4;279(Pt 3):135352. doi: 10.1016/j.ijbiomac.2024.135352.
Jintao Zhang 1,  Xinyu Fan 2,  Pengpeng Wang 1,  Rui Liang 1,  Donghan Wang 1,  Juan Xu 1,  Ding Zhang 1,  Yunfei Xie 1,  Qi Liao 1,  Zhe Jiao 3,  Yuejun Shi 4,  Guiqing Peng 5
Affiliations

Affiliations

  • 1 National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China; Hongshan Laboratory, Wuhan, China.
  • 2 Department of Biotechnology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
  • 3 National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China; Hongshan Laboratory, Wuhan, China. Electronic address: jiaozhe@mail.hzau.edu.cn.
  • 4 National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China; Hongshan Laboratory, Wuhan, China. Electronic address: shiyuejun2017@mail.hzau.edu.cn.
  • 5 National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China; Hongshan Laboratory, Wuhan, China. Electronic address: penggq@mail.hzau.edu.cn.
PMID: 39242012 DOI: 10.1016/j.ijbiomac.2024.135352
Abstract

Coronaviruses pose serious threats to human and animal health worldwide, of which their structural nucleocapsid (N) proteins play multiple key roles in viral replication. However, the structures of animal coronavirus N proteins are poorly understood, posing challenges for research on their functions and pathogenic mechanisms as well as the development of N protein-based Antiviral drugs. Therefore, N proteins must be further explored as potential Antiviral targets. We determined the structure of the NNTD of feline infectious peritonitis virus (FIPV) and identified 3,6-dihydroxyflavone (3,6- DHF) as an effective N protein inhibitor. 3,6-DHF successfully inhibited FIPV replication in CRFK cells, showing broad-spectrum activity and effectiveness against drugresistant strains. Our study provides important insights for developing novel broadspectrum anti-coronavirus drugs and treating infections caused by drug-resistant mutant strains.

Keywords

Antivirals; Broad-spectrum; Coronavirus; Nucleocapsid protein; Resistant.

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