2. Academic Validation
  3. Discovery of highly potent SARS-CoV-2 Mpro inhibitors based on benzoisothiazolone scaffold

Discovery of highly potent SARS-CoV-2 Mpro inhibitors based on benzoisothiazolone scaffold

  • Bioorg Med Chem Lett. 2022 Feb 15;58:128526. doi: 10.1016/j.bmcl.2022.128526.
Weixiong Chen 1,  Bo Feng 2,  Sheng Han 3,  Peipei Wang 3,  Wuhong Chen 3,  Yi Zang 4,  Jia Li 5,  Youhong Hu 6
Affiliations

Affiliations

  • 1 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 2 School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, No.103 Wenhua Road, Shenyang 110016, China.
  • 3 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 4 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China. Electronic address: [email protected].
  • 5 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, No.103 Wenhua Road, Shenyang 110016, China; Open Studio for Druggability Research of Marine Natural Products, Pilot National Laboratory for Marine Science and Technology (Qingdao), 1 Wenhai Road, Aoshanwei Jimo, Qingdao 266237, China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China. Electronic address: [email protected].
  • 6 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China. Electronic address: [email protected].
PMID: 34998903 DOI: 10.1016/j.bmcl.2022.128526
Abstract

The COVID-19 pandemic has drastically impacted global economies and public health. Although vaccine development has been successful, it was not sufficient against more infectious mutant strains including the Delta variant indicating a need for alternative treatment strategies such as small molecular compound development. In this work, a series of SARS-CoV-2 main protease (Mpro) inhibitors were designed and tested based on the active compound from high-throughput diverse compound library screens. The most efficacious compound (16b-3) displayed potent SARS-CoV-2 Mpro inhibition with an IC50 value of 116 nM and selectivity against SARS-CoV-2 Mpro when compared to PLpro and RdRp. This new class of compounds could be used as potential leads for further optimization in anti COVID-19 drug discovery.

Keywords

Benzoisothiazolone; COVID-19; Main protease inhibitors; SARS-CoV-2.

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