2. Academic Validation
  3. Exploring anti-SARS-CoV-2 natural products: dual-viral target inhibition by delphinidin and the anti-coronaviral efficacy of deapio platycodin D

Exploring anti-SARS-CoV-2 natural products: dual-viral target inhibition by delphinidin and the anti-coronaviral efficacy of deapio platycodin D

  • Nat Prod Bioprospect. 2025 Jun 13;15(1):39. doi: 10.1007/s13659-025-00523-w.
Jiani Lu # 1 2,  Yan Tang # 3,  Hongtao Li # 1 2,  Saisai Tian 1 4,  Xixiang Chen 1,  Xueyue Song 5,  Pengcheng Qin 1 2 6,  Jianrong Xu 1,  Haiyan Zhu 5,  Liqiang Ni 7,  Huarong Du 8,  Weidong Zhang 9 10 11,  Weihua Li 12,  Lili Chen 13 14 15
Affiliations

Affiliations

  • 1 The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 2 Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 3 Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
  • 4 School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
  • 5 Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
  • 6 School of Pharmacy, Henan University, Kaifeng, 475001, China.
  • 7 Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 8 Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. huarongdu2017@shutcm.edu.cn.
  • 9 The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. wdzhangy@hotmail.com.
  • 10 School of Pharmacy, Second Military Medical University, Shanghai, 200433, China. wdzhangy@hotmail.com.
  • 11 School of Pharmacy, Henan University, Kaifeng, 475001, China. wdzhangy@hotmail.com.
  • 12 Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China. whli@ecust.edu.cn.
  • 13 The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. llchen@shutcm.edu.cn.
  • 14 Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. llchen@shutcm.edu.cn.
  • 15 Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China. llchen@shutcm.edu.cn.
  • # Contributed equally.
PMID: 40512442 DOI: 10.1007/s13659-025-00523-w
Abstract

Qingfei Paidu decoction (QFPDD) has been extensively used in clinical treatments during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic. SARS-CoV-2 primarily invades host cells via its spike (S) protein binding to the angiotensin-converting enzyme 2 (ACE2) on the cell membrane, mediating viral-host membrane fusion. Blocking viral entry is a crucial step in preventing Infection, with the interaction between the S receptor binding domain (S-RBD) and ACE2 being a key Antiviral target. Given that SARS-CoV-2 predominantly affects the respiratory system and approximately 25% of patients suffering from corona virus disease 2019 (COVID-19) with gastrointestinal symptoms, we are committed to identifying more active ingredients in QFPDD that target the respiratory and gastrointestinal tracts of COVID-19 patients. Among medicinal Plants, ephedra and liquorice derived from QFPDD, along with two Other Chinese herbs, Platycodon grandiflorum and Radix Rhei Et Rhizome (rhubarb), have garnered our interest. These herbs have historically been used in traditional Chinese medicine (TCM) for treating infectious diseases with respiratory and digestive symptoms. Here, we established a library containing all components of the four individual herbs gathered from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and performed structure-based virtual screening to identify potential ACE2/S-RBD inhibitors. Subsequently, we selected 10 ingredients from the top 30 candidates and evaluated their activities using a pseudovirus neutralization assay. Delphinidin and deapio platycodin D (DPD) showed significant Antiviral potential with half-maximal inhibitory concentration (IC50) values of 45.35 µM and 1.38 µM, respectively. Furthermore, delphinidin also inhibited the 3-chymotrypsin-like protease (3CLpro), indicating its dual-viral target inhibitory potential. Notably, DPD effectively suppressed HCoV-229E replication in BEL-7402 cells. This study not only provides a strategy for rapid identifying Antiviral agents from TCM in anticipation of future pandemics but also offers theoretical and experimental evidence to support for the clinical use of QFPDD.

Keywords

Deapio platycodin D; Delphinidin; Qingfei Paidu decoction (QFPDD); S-RBD; SARS-CoV-2.

Figures
Products