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An extended conformation of SARS-CoV-2 main protease reveals allosteric targets.
Sun, Zengchao; Wang, Lu; Li, Xiyang; Fan, Chengpeng; Xu, Jianfeng; Shi, Zhenzhong; Qiao, Huarui; Lan, Zhongyun; Zhang, Xin; Li, Lingyun; Zhou, Xin; Geng, Yong.
  • Sun Z; The Chinese Academy of Sciences Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Wang L; Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
  • Li X; The Chinese Academy of Sciences Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Fan C; The Chinese Academy of Sciences Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Xu J; School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
  • Shi Z; Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
  • Qiao H; Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
  • Lan Z; Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
  • Zhang X; Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
  • Li L; Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
  • Zhou X; The Chinese Academy of Sciences Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Geng Y; Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
Proc Natl Acad Sci U S A ; 119(15): e2120913119, 2022 04 12.
Article in English | MEDLINE | ID: covidwho-1758464
ABSTRACT
SignificanceThe coronavirus main protease (Mpro) is required for viral replication. Here, we obtained the extended conformation of the native monomer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Mpro by trapping it with nanobodies and found that the catalytic domain and the helix domain dissociate, revealing allosteric targets. Another monomeric state is termed compact conformation and is similar to one protomer of the dimeric form. We designed a Nanoluc Binary Techonology (NanoBiT)-based high-throughput allosteric inhibitor assay based on structural conformational change. Our results provide insight into the maturation, dimerization, and catalysis of the coronavirus Mpro and pave a way to develop an anticoronaviral drug through targeting the maturation process to inhibit the autocleavage of Mpro.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Protease Inhibitors / Coronavirus 3C Proteases / SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2022 Document Type: Article Affiliation country: Pnas.2120913119

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Protease Inhibitors / Coronavirus 3C Proteases / SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2022 Document Type: Article Affiliation country: Pnas.2120913119