2. Academic Validation
  3. Perilla (Perilla frutescens) leaf extract inhibits SARS-CoV-2 via direct virus inactivation

Perilla (Perilla frutescens) leaf extract inhibits SARS-CoV-2 via direct virus inactivation

  • Biomed J. 2021 Jun;44(3):293-303. doi: 10.1016/j.bj.2021.01.005.
Wen-Fang Tang 1,  Hui-Ping Tsai 2,  Yu-Hsiu Chang 2,  Tein-Yao Chang 2,  Chung-Fan Hsieh 1,  Chia-Yi Lin 1,  Guan-Hua Lin 1,  Yu-Li Chen 3,  Jia-Rong Jheng 4,  Ping-Cheng Liu 2,  Chuen-Mi Yang 2,  Yuan-Fan Chin 2,  Cheng Cheung Chen 5,  Jyh-Hwa Kau 2,  Yi-Jen Hung 2,  Po-Shiuan Hsieh 2,  Jim-Tong Horng 6
Affiliations

Affiliations

  • 1 Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan.
  • 2 Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan.
  • 3 Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan.
  • 4 Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan.
  • 5 Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.
  • 6 Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: [email protected].
PMID: 34119448 DOI: 10.1016/j.bj.2021.01.005
Abstract

Background: While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Infection presents with mild or no symptoms in most cases, a significant number of patients become critically ill. Remdesivir has been approved for the treatment of coronavirus disease 2019 (COVID-19) in several countries, but its use as monotherapy has not substantially lowered mortality rates. Because agents from traditional Chinese medicine (TCM) have been successfully utilized to treat pandemic and endemic diseases, we designed the current study to identify novel anti-SARS-CoV-2 agents from TCM.

Methods: We initially used an antivirus-induced cell death assay to screen a panel of herbal extracts. The inhibition of the viral Infection step was investigated through a time-of-drug-addition assay, whereas a plaque reduction assay was carried out to validate the Antiviral activity. Direct interaction of the candidate TCM compound with viral particles was assessed using a viral inactivation assay. Finally, the potential synergistic efficacy of remdesivir and the TCM compound was examined with a combination assay.

Results: The herbal medicine Perilla leaf extract (PLE, approval number 022427 issued by the Ministry of Health and Welfare, Taiwan) had EC50 of 0.12 ± 0.06 mg/mL against SARS-CoV-2 in Vero E6 cells - with a selectivity index of 40.65. Non-cytotoxic PLE concentrations were capable of blocking viral RNA and protein synthesis. In addition, they significantly decreased virus-induced cytokine release and viral protein/RNA levels in the human lung epithelial cell line Calu-3. PLE inhibited viral replication by inactivating the virion and showed additive-to-synergistic efficacy against SARS-CoV-2 when used in combination with remdesivir.

Conclusion: Our results demonstrate for the first time that PLE is capable of inhibiting SARS-CoV-2 replication by inactivating the virion. Our data may prompt additional investigation on the clinical usefulness of PLE for preventing or treating COVID-19.

Keywords

COVID-19; Coronavirus; Perilla frutescens (L.) Britt; SARS-CoV-2; Traditional Chinese medicine; Zisu.

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