A traditional Chinese medicine formula NRICM101 to target COVID-19 through multiple pathways: A bedside-to-bench study

Biomed Pharmacother. 2021 Jan:133:111037. doi: 10.1016/j.biopha.2020.111037. Epub 2020 Nov 19.

Authors

Keng-Chang Tsai¹, Yi-Chia Huang², Chia-Ching Liaw³, Chia-I Tsai⁴, Chun-Tang Chiou⁵, Chien-Jung Lin⁶, Wen-Chi Wei⁷, Sunny Jui-Shan Lin⁸, Yu-Hwei Tseng⁹, Kuo-Ming Yeh¹⁰, Yi-Ling Lin¹¹, Jia-Tsrong Jan¹², Jian-Jong Liang¹³, Chun-Che Liao¹⁴, Wen-Fei Chiou¹⁵, Yao-Haur Kuo¹⁶, Shen-Ming Lee¹⁷, Ming-Yung Lee¹⁸, Yi-Chang Su¹⁹

Affiliations

¹ National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No.155-1, Section 2, Linong Street, Beitou District, Taipei 11221, Taiwan; Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, No. 250 Wu-Xing Street, Taipei 11031, Taiwan. Electronic address: tkc@nricm.edu.tw.
² Department of Chinese Medicine, Tri-Service General Hospital, National Defense Medical Center, No.325, Section 2, Chenggong Road, Neihu District, Taipei 11490, Taiwan. Electronic address: hec62918@mail.ndmctsgh.edu.tw.
³ National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No.155-1, Section 2, Linong Street, Beitou District, Taipei 11221, Taiwan. Electronic address: liawcc@nricm.edu.tw.
⁴ Department of Traditional Chinese Medicine, Taichung Veterans General Hospital, No. 1650, Taiwan Boulevard Section 4, Seatwen District, Taichung 407204, Taiwan. Electronic address: citsai777@gmail.com.
⁵ National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No.155-1, Section 2, Linong Street, Beitou District, Taipei 11221, Taiwan. Electronic address: ctchiou@nricm.edu.tw.
⁶ Department of Chinese Medicine, Tri-Service General Hospital, National Defense Medical Center, No.325, Section 2, Chenggong Road, Neihu District, Taipei 11490, Taiwan. Electronic address: linchienjung@mail.ndmctsgh.edu.tw.
⁷ National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No.155-1, Section 2, Linong Street, Beitou District, Taipei 11221, Taiwan. Electronic address: jackwei@nricm.edu.tw.
⁸ Department of Chinese Medicine, Tri-Service General Hospital, National Defense Medical Center, No.325, Section 2, Chenggong Road, Neihu District, Taipei 11490, Taiwan. Electronic address: sunnylin@nricm.edu.tw.
⁹ National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No.155-1, Section 2, Linong Street, Beitou District, Taipei 11221, Taiwan. Electronic address: mayeeshat@nricm.edu.tw.
¹⁰ Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Chenggong Road, Neihu District, Taipei 11490, Taiwan. Electronic address: kmyeh@mail.ndmctsgh.edu.tw.
¹¹ Institute of Biomedical Sciences, Academia Sinica, No. 128, Section 2, Academia Road, Nankang District, Taipei 11529, Taiwan. Electronic address: yll@ibms.sinica.edu.tw.
¹² Genomic Research Center, Academia Sinica, No. 128, Section 2, Academia Road, Nankang District, Taipei, 11529, Taiwan. Electronic address: tsrong33@gate.sinica.edu.tw.
¹³ Institute of Biomedical Sciences, Academia Sinica, No. 128, Section 2, Academia Road, Nankang District, Taipei 11529, Taiwan. Electronic address: jjliang1234@yahoo.com.tw.
¹⁴ Institute of Biomedical Sciences, Academia Sinica, No. 128, Section 2, Academia Road, Nankang District, Taipei 11529, Taiwan. Electronic address: jfliao@ibms.sinica.edu.tw.
¹⁵ National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No.155-1, Section 2, Linong Street, Beitou District, Taipei 11221, Taiwan. Electronic address: wfchiou@nricm.edu.tw.
¹⁶ National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No.155-1, Section 2, Linong Street, Beitou District, Taipei 11221, Taiwan. Electronic address: kuoyh@nricm.edu.tw.
¹⁷ Department of Statistic, Feng Chia University, No. 100, Wenhwa Road, Seatwen District, Taichung 40724, Taiwan. Electronic address: smlee@mail.fcu.edu.tw.
¹⁸ Department of Data Science and Big Data Analytics, Providence University, Taichung, No. 200, Section 7, Taiwan Boulevard, Shalu District, Taichung 43301, Taiwan. Electronic address: mylee@pu.edu.tw.
¹⁹ National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No.155-1, Section 2, Linong Street, Beitou District, Taipei 11221, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung 40402, Taiwan. Electronic address: sychang@nricm.edu.tw.

Abstract

COVID-19 is a global pandemic, with over 50 million confirmed cases and 1.2 million deaths as of November 11, 2020. No therapies or vaccines so far are recommended to treat or prevent the new coronavirus. A novel traditional Chinese medicine formula, Taiwan Chingguan Yihau (NRICM101), has been administered to patients with COVID-19 in Taiwan since April 2020. Its clinical outcomes and pharmacology have been evaluated. Among 33 patients with confirmed COVID-19 admitted in two medical centers, those (n = 12) who were older, sicker, with more co-existing conditions and showing no improvement after 21 days of hospitalization were given NRICM101. They achieved 3 consecutive negative results within a median of 9 days and reported no adverse events. Pharmacological assays demonstrated the effects of the formula in inhibiting the spike protein/ACE2 interaction, 3CL protease activity, viral plaque formation, and production of cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. This bedside-to-bench study suggests that NRICM101 may disrupt disease progression through its antiviral and anti-inflammatory properties, offering promise as a multi-target agent for the prevention and treatment of COVID-19.

Keywords: 3CL protease; Cytokine storm; NRICM101; SARS-CoV-2; Spike protein; Traditional Chinese medicine.

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Angiotensin-Converting Enzyme 2 / drug effects
Antiviral Agents / therapeutic use*
Coronavirus 3C Proteases / drug effects
Drug Compounding
Drugs, Chinese Herbal / adverse effects
Drugs, Chinese Herbal / pharmacology
Drugs, Chinese Herbal / therapeutic use*
Female
Humans
Interleukin-6 / antagonists & inhibitors
Male
Medicine, Chinese Traditional
Middle Aged
Negative Results
Spike Glycoprotein, Coronavirus / drug effects
Treatment Outcome
Tumor Necrosis Factor-alpha / antagonists & inhibitors
Viral Plaque Assay
Young Adult

Substances

Antiviral Agents
Drugs, Chinese Herbal
IL6 protein, human
Interleukin-6
Spike Glycoprotein, Coronavirus
Tumor Necrosis Factor-alpha
ACE2 protein, human
Angiotensin-Converting Enzyme 2
Coronavirus 3C Proteases