A Chemical Strategy for the Degradation of the Main Protease of SARS-CoV-2 in Cells

  • J Am Chem Soc. 2023 Dec 20;145(50):27248-27253. doi: 10.1021/jacs.3c12678.
Xiaohong Sang  1 ,  Juan Wang  2 ,  Jiao Zhou  1 ,  Yan Xu  1 ,  Jing An  3 ,  Arieh Warshel  4 ,  Ziwei Huang  1  2  3
Affiliations
  • 1. Ciechanover Institute of Precision and Regenerative Medicine, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China.
  • 2. School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • 3. Division of Infectious Diseases and Global Public Health, Department of Medicine, School of Medicine, University of California San Diego, La Jolla, California 92037, United States.
  • 4. Department of Chemistry, University of Southern California, Los Angeles, California 90089, United States.
PMID: 38064654 DOI: 10.1021/jacs.3c12678
Abstract

SARS-CoV-2 is the virus that causes the global pandemic of COVID-19. The main protease (Mpro) of SARS-CoV-2 is essential for viral Infection and is one of the major therapeutic targets for COVID-19. Here, we report the design, synthesis, and biological characterization of a novel heterobifunctional small molecule that could effectively induce the degradation of SARS-CoV-2 Mpro and its drug-resistant mutants in HEK 293T cells, thus demonstrating a new alternative strategy for intervening with proteins important for this novel coronavirus.

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