Honeysuckle extracts as a potential inhibitor of SARS-CoV-2 infection

Ping-Chang Lin; Ying-Ray Lee; Li-Teh Liu; Shyh-Shin Chiou; Po-Chih Chen; Ching-Yi Tsai; Jih-Jin Tsai

doi:10.3389/fphar.2025.1517585

Honeysuckle extracts as a potential inhibitor of SARS-CoV-2 infection

Front Pharmacol. 2025 Apr 16:16:1517585. doi: 10.3389/fphar.2025.1517585. eCollection 2025.

Authors

Ping-Chang Lin^#¹, Ying-Ray Lee^#^{2

3

4

5}, Li-Teh Liu⁶, Shyh-Shin Chiou^{7

8

9

10}, Po-Chih Chen^{11

12}, Ching-Yi Tsai¹, Jih-Jin Tsai^{1

13

14}

Affiliations

¹ Tropical Medicine Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
² Department of Microbiology and Immunology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ Master of Science Program in Tropical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁴ Faculty of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁵ Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁶ Department of Medical Laboratory Science and Biotechnology, College of Medical Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan.
⁷ Taiwan Society of Thrombosis and Hemostasis (TSTH) Study Group, Taipei, Taiwan.
⁸ Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁹ Division of Pediatric Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
¹⁰ Center of Applied Genomics, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹¹ Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
¹² Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹³ School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹⁴ Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

^# Contributed equally.

Abstract

Background: In the current era of coronavirus disease 2019 (COVID-19), we were interested in searching for medications other than the currently available antiviral drugs Paxlovid and Molnupiravir that cause minimal side effects and do not harm the human body. Honeysuckle extract (HSE) is a traditional Chinese medicine (TCM) that has been shown to exert antiviral effects in other studies. However, no studies have indicated whether HSE has an inhibitory effect on SARS-CoV-2.

Methods: We prepared HSEs from dried honeysuckle flowers. We performed a cell viability assay, median tissue culture infection dose (TCID₅₀) assay, and qRT‒PCR, and calculated the virus titers using the Reed-Muench method to evaluate the inhibitory effects of aqueous and alcohol HSEs on SARS‒CoV‒2 and explore the possible underlying mechanisms.

Results: In this study, post-treatment with HSE resulted in dose-dependent decreases in both the RNA levels and TCID₅₀ of SARS-CoV-2 in Vero E6 cells; treatment with 50 μg/ml and 100 μg/ml alcohol HSEs achieved up to 95.323% and 92.587% inhibition, respectively. Moreover, pre-treatment with aqueous HSEs effectively reduced the RNA levels, and TCID₅₀ of SARS-CoV-2 by up to 99.684%, and alcohol HSEs achieved up to 99.921% inhibition; both of these effects occurred in a dose-dependent manner.

Conclusion: The results suggest that HSEs may have the potential to prevent SARS-CoV-2 infection.

Keywords: COVID-19; Lonicera japonica Thunb.; SARS-CoV-2; extracts; honeysuckle.