2. Academic Validation
  3. Merbromin is a mixed-type inhibitor of 3-chyomotrypsin like protease of SARS-CoV-2

Merbromin is a mixed-type inhibitor of 3-chyomotrypsin like protease of SARS-CoV-2

  • Biochem Biophys Res Commun. 2022 Feb 5:591:118-123. doi: 10.1016/j.bbrc.2021.12.108.
Junjie Chen 1,  Yaya Zhang 2,  Dequan Zeng 1,  Bingchang Zhang 2,  Xiaohong Ye 1,  Zhiping Zeng 1,  Xiao-Kun Zhang 1,  Zhanxiang Wang 3,  Hu Zhou 4
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, China; High Throughput Drug Screening Platform of Xiamen University, China.
  • 2 Department of Neurosurgery, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, China.
  • 3 Department of Neurosurgery, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, China; School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China. Electronic address: WangZX@xmu.edu.cn.
  • 4 School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, China; High Throughput Drug Screening Platform of Xiamen University, China. Electronic address: huzhou@xmu.edu.cn.
PMID: 35007835 DOI: 10.1016/j.bbrc.2021.12.108
Abstract

3-chyomotrypsin like protease (3CLpro) has been considered as a promising target for developing anti-SARS-CoV-2 drugs. Herein, about 6000 compounds were analyzed by high-throughput screening using Enzyme activity model, and Merbromin, an Antibacterial agent, was identified as a potent inhibitor of 3CLpro. Merbromin strongly inhibited the proteolytic activity of 3CLpro but not the Other three proteases Proteinase K, Trypsin and Papain. Michaelis-Menten kinetic analysis showed that Merbromin was a mixed-type inhibitor of 3CLpro, due to its ability of increasing the KM and decreasing the Kcat of 3CLpro. The binding assays and molecular docking suggested that 3CLpro possessed two binding sites for Merbromin. Consistently, Merbromin showed a weak binding to the Other three proteases. Together, these findings demonstrated that Merbromin is a selective inhibitor of 3CLpro and provided a scaffold to design effective inhibitors of SARS-CoV-2.

Keywords

3CLpro; High-throughput screening; Inhibitor; Merbromin; Protease; SARS-CoV-2.

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