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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Screening of Medicinal Herbs Identifies Cimicifuga foetida and Its Bioactive Component Caffeic Acid as SARS-CoV-2 Entry Inhibitors

by
Ching-Hsuan Liu
1,2,†,
Yu-Ting Kuo
2,3,4,†,
Chien-Ju Lin
5,
Feng-Lin Yen
6,7,8,
Shu-Jing Wu
9 and
Liang-Tzung Lin
1,10,*
1
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
2
Department of Diagnostic Imaging, Chi Mei Medical Center, Tainan 710, Taiwan
3
Institute of Precision Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 804, Taiwan
4
Department of Radiology, School and College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
5
School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
6
Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
7
Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan
8
Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
9
Department of Nutritional Health, Chia-Nan University of Pharmacy and Science, Tainan 717, Taiwan
10
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
*
Author to whom correspondence should be addressed.
†
These authors share first authorship.
Viruses 2025, 17(8), 1086; https://doi.org/10.3390/v17081086
Submission received: 19 June 2025 / Revised: 28 July 2025 / Accepted: 1 August 2025 / Published: 5 August 2025
(This article belongs to the Section Coronaviruses)
Versions Notes

Abstract

The emergence of SARS-CoV-2 variants highlights the urgent need for novel therapeutic strategies, particularly entry inhibitors that could efficiently prevent viral infection. Medicinal herbs and herbal combination formulas have long been recognized for their effects in treating infectious diseases and their antiviral properties, thus providing abundant resources for the discovery of antiviral candidates. While many candidates have been suggested to have antiviral activity against SARS-CoV-2 infection, few have been validated for their mechanisms, including possible effects on viral entry. This study aimed to identify SARS-CoV-2 entry inhibitors from medicinal herbs and herbal formulas that are known for heat-clearing and detoxifying properties and/or antiviral activities. A SARS-CoV-2 pseudoparticle (SARS-CoV-2pp) system was used to assess mechanism-specific entry inhibition. Our results showed that the methanol extract of Anemarrhena asphodeloides rhizome, as well as the water extracts of Cimicifuga foetida rhizome, Xiao Chai Hu Tang (XCHT), and Sheng Ma Ge Gen Tang (SMGGT), have substantial inhibitory effects on the entry of SARS-CoV-2pps into host cells. Given the observation that Cimicifuga foetida exhibited the most potent inhibition and is a constituent of SMGGT, we further investigated the major compounds of the herb and identified caffeic acid as a bioactive component for blocking SARS-CoV-2pp entry. Entry inhibition of Cimicifuga foetida and caffeic acid was validated on both wild-type and the currently dominant JN.1 strain SARS-CoV-2pp systems. Moreover, caffeic acid was able to both inactivate the pseudoparticles and prevent their entry into pretreated host cells. The results support the traditional use of these herbal medicines and underscore their potential as valuable resources for identifying active compounds and developing therapeutic entry inhibitors for the management of COVID-19.
Keywords: SARS-CoV-2; medicinal herbs; herbal formulas; entry inhibitor; pseudoparticle; antiviral SARS-CoV-2; medicinal herbs; herbal formulas; entry inhibitor; pseudoparticle; antiviral

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MDPI and ACS Style

Liu, C.-H.; Kuo, Y.-T.; Lin, C.-J.; Yen, F.-L.; Wu, S.-J.; Lin, L.-T. Screening of Medicinal Herbs Identifies Cimicifuga foetida and Its Bioactive Component Caffeic Acid as SARS-CoV-2 Entry Inhibitors. Viruses 2025, 17, 1086. https://doi.org/10.3390/v17081086

AMA Style

Liu C-H, Kuo Y-T, Lin C-J, Yen F-L, Wu S-J, Lin L-T. Screening of Medicinal Herbs Identifies Cimicifuga foetida and Its Bioactive Component Caffeic Acid as SARS-CoV-2 Entry Inhibitors. Viruses. 2025; 17(8):1086. https://doi.org/10.3390/v17081086

Chicago/Turabian Style

Liu, Ching-Hsuan, Yu-Ting Kuo, Chien-Ju Lin, Feng-Lin Yen, Shu-Jing Wu, and Liang-Tzung Lin. 2025. "Screening of Medicinal Herbs Identifies Cimicifuga foetida and Its Bioactive Component Caffeic Acid as SARS-CoV-2 Entry Inhibitors" Viruses 17, no. 8: 1086. https://doi.org/10.3390/v17081086

APA Style

Liu, C.-H., Kuo, Y.-T., Lin, C.-J., Yen, F.-L., Wu, S.-J., & Lin, L.-T. (2025). Screening of Medicinal Herbs Identifies Cimicifuga foetida and Its Bioactive Component Caffeic Acid as SARS-CoV-2 Entry Inhibitors. Viruses, 17(8), 1086. https://doi.org/10.3390/v17081086

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