2. Academic Validation
  3. In vitro enzyme characterization and several inhibitors for monkeypox virus core protease I7L

In vitro enzyme characterization and several inhibitors for monkeypox virus core protease I7L

  • FEMS Microbiol Lett. 2025 Jan 10:372:fnaf008. doi: 10.1093/femsle/fnaf008.
Lin Wei 1 2,  Yuqi Wu 1,  Shuai Li 1,  Jun Weng 1 3,  Miaomiao Geng 1,  Meng Mei 1 2,  Zigong Wei 1 2 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, College of Life Sciences, Hubei University, Wuhan 430062, China.
  • 2 Hubei Jiangxia Laboratory, Wuhan 430207, China.
  • 3 Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
  • 4 National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, College of Life Sciences, Hubei University, Wuhan 430062, China.
PMID: 39824654 DOI: 10.1093/femsle/fnaf008
Abstract

Monkeypox is a zoonotic viral disease caused by the monkeypox virus, a member of the genus Orthopoxvirus within the family Poxviridae, which also includes the variola virus. On 14 August 2024, WHO Director-General declared monkeypox outbreak a public health emergency of international concern. Similar to variola virus core protease K7L, I7L could be identified as a promising target to fight against monkeypox virus. Our work provides a solid foundation as well as specific molecular tools (protease production methods, assay design, inhibitor design) that can now be used to probe the function of I7L in vitro. Notably, in this work, various reported covalent lead compounds for COVID-19 proteases were screened and A68, shikonin, and myricetin were identified as exhibiting high inhibitory activity against I7L. This work not only sheds light on effective inhibitors for the monkeypox virus core protease but also contributes to the broader search for Antiviral agents targeting this Enzyme.

Keywords

I7L; covalent inhibitor; monkeypox virus (MPXV); myricetin; shikonin.

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