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

doi:10.1007/s13659-025-00523-w

Natural Products and Bioprospecting ›› 2025, Vol. 15 ›› Issue (4): 39-39.DOI: 10.1007/s13659-025-00523-w

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

Jiani Lu^1,2, Yan Tang³, Hongtao Li^1,2, Saisai Tian^1,4, Xixiang Chen¹, Xueyue Song⁶, Pengcheng Qin^1,2,5, Jianrong Xu¹, Haiyan Zhu⁶, Liqiang Ni⁷, Huarong Du⁷, Weidong Zhang^1,4,5, Weihua Li³, Lili Chen^1,2,3

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. School of Pharmacy, Henan University, Kaifeng, 475001, China;
6. Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai, 201203, China;
7. Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

Received:2025-03-25 Accepted:2025-05-21 Online:2025-06-13 Published:2025-08-23
Supported by:
This work was supported by the Shanghai Municipal Science and Technology Major Project (ZD2021CY001), the Shanghai Oriental Talent Program for Top-notch Project (No. BJWS2024068), the National Key Research and Development Program of China (2023YFC3503400, 2022YFC3502000), the SIMM-SHUTCM Traditional Chinese Medicine Innovation Joint Research Program (E2G805H), and the National Natural Science Foundation of China (82141203).

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

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. School of Pharmacy, Henan University, Kaifeng, 475001, China;
6. Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai, 201203, China;
7. Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

通讯作者: Huarong Du, E-mail:huarongdu2017@shutcm.edu.cn;Weidong Zhang, E-mail:wdzhangy@hotmail.com;Weihua Li, E-mail:whli@ecust.edu.cn;Lili Chen, E-mail:llchen@shutcm.edu.cn
基金资助:
This work was supported by the Shanghai Municipal Science and Technology Major Project (ZD2021CY001), the Shanghai Oriental Talent Program for Top-notch Project (No. BJWS2024068), the National Key Research and Development Program of China (2023YFC3503400, 2022YFC3502000), the SIMM-SHUTCM Traditional Chinese Medicine Innovation Joint Research Program (E2G805H), and the National Natural Science Foundation of China (82141203).

Abstract

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 (3CL^pro), 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.

Key words: Qingfei Paidu decoction (QFPDD), SARS-CoV-2, S-RBD, Delphinidin, Deapio platycodin D

摘要： 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 (3CL^pro), 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.

关键词: Qingfei Paidu decoction (QFPDD), SARS-CoV-2, S-RBD, Delphinidin, Deapio platycodin D

Jiani Lu, Yan Tang, Hongtao Li, Saisai Tian, Xixiang Chen, Xueyue Song, Pengcheng Qin, Jianrong Xu, Haiyan Zhu, Liqiang Ni, Huarong Du, Weidong Zhang, Weihua Li, Lili Chen. Exploring anti-SARS-CoV-2 natural products: dual-viral target inhibition by delphinidin and the anti-coronaviral efficacy of deapio platycodin D[J]. Natural Products and Bioprospecting, 2025, 15(4): 39-39.

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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

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