1. Academic Validation
  2. Identification of a conserved G-quadruplex within the E165R of African swine fever virus (ASFV) as a potential antiviral target

Identification of a conserved G-quadruplex within the E165R of African swine fever virus (ASFV) as a potential antiviral target

  • J Biol Chem. 2024 Jun 7;300(7):107453. doi: 10.1016/j.jbc.2024.107453.
Wenhao Liu 1 Xinglin He 2 Yance Zhu 1 Yaqin Li 3 Zhihao Wang 1 Pengfei Li 2 Jiajia Pan 1 Jiang Wang 1 Beibei Chu 1 Guoyu Yang 1 Mengjia Zhang 2 Qigai He 2 Yongtao Li 4 Wentao Li 5 Chao Zhang 6
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou, China; Key Laboratory of Animal Growth and Development of Henan Province, Henan Agricultural University, Zhengzhou, China.
  • 2 National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Hubei Hongshan Laboratory, Wuhan, China.
  • 3 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China.
  • 4 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China. Electronic address: yongtaole@126.com.
  • 5 National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Hubei Hongshan Laboratory, Wuhan, China. Electronic address: wentao@mail.hzau.edu.cn.
  • 6 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou, China; Key Laboratory of Animal Growth and Development of Henan Province, Henan Agricultural University, Zhengzhou, China. Electronic address: chaozhang@henau.edu.cn.
Abstract

Identification of a conserved G-quadruplex in E165R of ASFVAfrican swine fever virus (ASFV) is a double-stranded DNA arbovirus with high transmissibility and mortality rates. It has caused immense economic losses to the global pig industry. Currently, no effective vaccines or medications are to combat ASFV Infection. G-quadruplex (G4) structures have attracted increasing interest because of their regulatory role in vital biological processes. In this study, we identified a conserved G-rich sequence within the E165R gene of ASFV. Subsequently, using various methods, we verified that this sequence could fold into a parallel G4. In addition, the G4-stabilizers pyridostatin and 5,10,15,20-tetrakis-(N-methyl-4-pyridyl) porphin (TMPyP4) can bind and stabilize this G4 structure, thereby inhibiting E165R gene expression, and the inhibitory effect is associated with G4 formation. Moreover, the G4 ligand pyridostatin substantially impeded ASFV proliferation in Vero cells by reducing gene copy number and viral protein expression. These compelling findings suggest that G4 structures may represent a promising and novel Antiviral target against ASFV.

Keywords

ASFV; African swine fever virus; G-quadruplex; G4 ligands; antiviral activity.

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