BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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The N-terminal peptide of the main protease of SARS-CoV-2, targeting dimer interface, inhibits its proteolytic activity

  • Sunyu Song (Department of Biological Sciences, Konkuk University) ;
  • Yeseul Kim (Department of Biological Sciences, Konkuk University) ;
  • Kiwoong Kwak (Department of Biological Sciences, Konkuk University) ;
  • Hyeonmin Lee (Department of Biological Sciences, Konkuk University) ;
  • Hyunjae Park (Department of Biological Sciences, Konkuk University) ;
  • Young Bong Kim (Department of Biomedical Science and Engineering, Konkuk University) ;
  • Hee-Jung Lee (Department of Biomedical Science and Engineering, Konkuk University) ;
  • Lin-Woo Kang (Department of Biological Sciences, Konkuk University)
  • 투고 : 2023.08.21
  • 심사 : 2023.09.20
  • 발행 : 2023.11.30
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초록

The main protease (Mpro) of SARS-CoV-2 cleaves 11 sites of viral polypeptide chains and generates essential non-structural proteins for viral replication. Mpro is an important drug target against COVID-19. In this study, we developed a real-time fluorometric turn-on assay system to evaluate Mpro proteolytic activity for a substrate peptide between NSP4 and NSP5. It produced reproducible and reliable results suitable for HTS inhibitor assays. Thus far, most inhibitors against Mpro target the active site for substrate binding. Mpro exists as a dimer, which is essential for its activity. We investigated the potential of the Mpro dimer interface to act as a drug target. The dimer interface is formed of domain II and domain III of each protomer, in which N-terminal ten amino acids of the domain I are bound in the middle as a sandwich. The N-terminal part provides approximately 39% of the dimer interface between two protomers. In the real-time fluorometric turn-on assay system, peptides of the N-terminal ten amino acids, N10, can inhibit the Mpro activity. The dimer interface could be a prospective drug target against Mpro. The N-terminal sequence can help develop a potential inhibitor.

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과제정보

This research was supported by a grant (22212MFDS254) from the Ministry of Food and Drug Safety and by the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2017M3A9E4078017).

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