2. Academic Validation
  3. Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19

Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19

  • Proc Natl Acad Sci U S A. 2023 May 2;120(18):e2301775120. doi: 10.1073/pnas.2301775120.
Haiyu Xu 1,  Shufen Li 2,  Jiayuan Liu 3,  Jinlong Cheng 4,  Liping Kang 5,  Weijie Li 1,  Yute Zhong 1,  Chaofa Wei 5,  Lifeng Fu 4,  Jianxun Qi 4 6,  Yulan Zhang 2,  Miaomiao You 2,  Zhenxing Zhou 2,  Chongtao Zhang 2,  Haixia Su 3,  Sheng Yao 3,  Zhaoyin Zhou 3,  Yulong Shi 3,  Ran Deng 7,  Qi Lv 7,  Fengdi Li 7,  Feifei Qi 7,  Jie Chen 1,  Siqin Zhang 8,  Xiaojing Ma 5,  Zhijian Xu 3,  Shao Li 8,  Yechun Xu 3,  Ke Peng 2,  Yi Shi 4 6,  Hualiang Jiang 3,  George F Gao 4 6,  Luqi Huang 5
Affiliations

Affiliations

  • 1 Institute of Chinese Materia Medica, Academy of Chinese Medical Sciences, Beijing 100700, China.
  • 2 State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430207, China.
  • 3 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 4 Chinese Academy of Sciences (CAS) Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • 5 State Key Laboratory of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
  • 6 Beijing Life Science Academy, Beijing 102209, China.
  • 7 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Key Laboratory of Comparative Medicine for Human Diseases of the National Health Commission, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
  • 8 Institute for Traditional Chinese Medicine-X, Ministry of Education Key Laboratory of Bioinformatics/Bioinformatics Division, Beijing National Research Center for Information Science and Technology, Department of Automation, Tsinghua University, Beijing 100084, China.
PMID: 37094153 DOI: 10.1073/pnas.2301775120
Abstract

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective Antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with Antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the Antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 Infection, including two inhibitors (echinatin and quercetin) of the main protease (Mpro), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed strong inhibitory activities against cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4). Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were determined at resolutions of 1.54 Å and 1.65 Å, respectively, and both compounds bind in the active site of PDE4 with similar interactions. These findings will greatly stimulate the study of TCMT-NDRD against COVID-19.

Keywords

COVID-19; TCMT-NDRD; anti-inflammation; antivirus; traditional Chinese medicine.

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