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Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients.
Su, Hai-Xia; Yao, Sheng; Zhao, Wen-Feng; Li, Min-Jun; Liu, Jia; Shang, Wei-Juan; Xie, Hang; Ke, Chang-Qiang; Hu, Hang-Chen; Gao, Mei-Na; Yu, Kun-Qian; Liu, Hong; Shen, Jing-Shan; Tang, Wei; Zhang, Lei-Ke; Xiao, Geng-Fu; Ni, Li; Wang, Dao-Wen; Zuo, Jian-Ping; Jiang, Hua-Liang; Bai, Fang; Wu, Yan; Ye, Yang; Xu, Ye-Chun.
  • Su HX; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Yao S; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Zhao WF; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Li MJ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Liu J; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Shang WJ; Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
  • Xie H; Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China.
  • Ke CQ; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Hu HC; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Gao MN; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
  • Yu KQ; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Liu H; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Shen JS; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Tang W; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Zhang LK; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Xiao GF; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Ni L; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Wang DW; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Zuo JP; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Jiang HL; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Bai F; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Wu Y; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Ye Y; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Xu YC; University of Chinese Academy of Sciences, Beijing, 100049, China.
Acta Pharmacol Sin ; 41(9): 1167-1177, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-691161
ABSTRACT
Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a "shield" in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Virus Replication / Flavonoids / Drugs, Chinese Herbal / Coronavirus Infections / Flavanones / Pandemics / Betacoronavirus Type of study: Prognostic study Topics: Traditional medicine Limits: Animals / Humans Language: English Journal: Acta Pharmacol Sin Journal subject: Pharmacology Year: 2020 Document Type: Article Affiliation country: S41401-020-0483-6

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Virus Replication / Flavonoids / Drugs, Chinese Herbal / Coronavirus Infections / Flavanones / Pandemics / Betacoronavirus Type of study: Prognostic study Topics: Traditional medicine Limits: Animals / Humans Language: English Journal: Acta Pharmacol Sin Journal subject: Pharmacology Year: 2020 Document Type: Article Affiliation country: S41401-020-0483-6