key: cord-0787716-fp48asjs authors: Wang, Zhonglei; Yang, Liyan title: Chinese herbal medicine: Fighting SARS-CoV-2 infection on all fronts date: 2021-01-21 journal: J Ethnopharmacol DOI: 10.1016/j.jep.2021.113869 sha: 6216081d91a41d7e1f667ef239c730abb9727f05 doc_id: 787716 cord_uid: fp48asjs ETHNOPHARMACOLOGICAL RELEVANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), a highly pathogenic virus that has spread rapidly across the entire world. There is a critical need to develop safe and effective drugs, especially broad-spectrum antiviral and organ protection agents in order to treat and prevent this dangerous disease. It is possible that Chinese herbal medicine may play an essential role in the treatment of patients with SARS-CoV-2 infection. Aim of the review: We aim to review the use of Chinese herbal medicine in the treatment of COVID-19 both in vitro and in clinical practice. Our goal was to provide a better understanding of the potential therapeutic effects of Chinese herbal medicine and to establish a "Chinese protocol" for the treatment of COVID-19. MATERIALS AND METHODS: We systematically reviewed published research relating to traditional Chinese herbal medicines and the treatment of SARS-CoV-2 from inception to the 6(th) January 2021 by screening a range of digital databases (Web of Science, bioRxiv, medRxiv, China National Knowledge Infrastructure, X-MOL, Wanfang Data, Google Scholar, PubMed, Elsevier, and other resources) and public platforms relating to the management of clinical trials. We included the active ingredients of Chinese herbal medicines, monomer preparations, crude extracts, and formulas for the treatment of COVID-19. 6, 2021. RESULTS: In mainland China, a range of Chinese herbal medicines have been recognized as very promising anti-SARS-CoV-2 agents, including active ingredients (quercetagetin, osajin, tetrandrine, proscillaridin A, and dihydromyricetin), monomer preparations (xiyanping injection, matrine-sodium chloride injection, diammonium glycyrrhizinate enteric-coated capsules, and sodium aescinate injection), crude extracts (Scutellariae Radix extract and garlic essential oil), and formulas (Qingfei Paidu decoction, Lianhuaqingwen capsules, and Pudilan Xiaoyan oral liquid). All these agents have potential activity against SARS-CoV-2 and have attracted significant attention due to their activities both in vitro and in clinical practice. CONCLUSIONS: As a key component of the COVID-19 treatment regimen, Chinese herbal medicines have played an irreplaceable role in the treatment of SARS-CoV-2 infection. The "Chinese protocol" has already demonstrated clear clinical importance. The use of Chinese herbal medicines that are capable of inhibiting SARS-Cov-2 infection may help to address this immediate unmet clinical need and may be attractive to other countries that are also seeking new options for effective COVID-19 treatment. Our analyses suggest that countries outside of China should also consider protocols involving Chinese herbal medicines combat this fast-spreading viral infection. concerted effort to combat SARS-CoV-2 infection, including Chinese medicine practitioners. 114 The outstanding performance of Chinese herbal medicine, especially in mainland China, has 115 led to the publication of several interesting reviews on COVID-19 from the perspectives of The molecule (active ingredient) is responsible for the biological activity of Chinese herbal 123 medicine. To better digest the potential therapeutic effects of Chinese herbal medicine, we 124 attempted to focus on both representative and different categories of chemical components 125 (involving high-quality anti-SARS-CoV-2 studies in vitro), rather than take a systematically driven 126 approach. We also emphasize the unique advantages of Chinese herbal medicines in terms of 127 organ protection and broad-spectrum activity against viruses. 128 This review presents a hierarchical overview of the current progress in potentially active 129 anti-SARS-CoV-2 ingredients in Chinese herbal medicine, monomer preparations, crude extracts, 130 and formulas. Our aim was to provide a 'Chinese protocol' for the treatment of COVID-19. 131 132 The history of the modern pharmaceutical industry includes many anecdotes describing how 135 traditional Chinese medicine inspired the discovery of several drugs; for example, artemisinin (Ma 136 et al., 2020c) and arsenic trioxide (List et al., 2003) . Chinese herbal medicine consists of a large 137 group of secondary metabolites (e.g., flavonoids) that present wide structural diversity and 138 includes a range of compounds (e.g., flavones, flavanols, flavanonols, and isoflavones) that 139 mediate a wide range of valuable bioactivities, including anti-browning, anti-tuberculosis, 140 anti-microbial, anti-cancer and anti-oxidant effects . As research continues, 141 flavonoids have recently been recognized as promising antiviral agents against multiple viruses, 142 10 / 52 52 52 52 In order to support the precision design of a drug against SARS-Cov-2, Li Phillyrin, a form of bisepoxylignan, can be extracted from the traditional Chinese medicine 257 Forsythia suspensa (Thunb.) (Fig. 2E ) (Xia et al., 2010) . Literature shows that phillyrin exhibits 258 promising pharmacological properties against lung inflammation (Zhong et al., 2013) , traumatic 259 brain injury (Jiang et al., 2020) and acute kidney injury (Zhang et al., 2020b) . Yang et al. recently 260 revealed that phillyrin could effectively inhibit the replication of SARS-CoV-2 in Vero E6 cells at 261 an IC 50 of 63.90 μg/mL with a low toxicity profile (SI = 30.66) by inhibiting activation of the 262 nuclear factor kappa B (NF-κB) signaling pathway (Ma et al., 2020d) . Furthermore, network 263 pharmacology and molecular docking analysis further revealed that phillyrin could block the 264 binding of SARS-CoV-2 S-protein and Gln325 in ACE2 (Yu et al., 2020a) . 265 Our growing understanding of the processes that can be used to identify potential 266 anti-SARS-CoV-2 molecules has led to the use of active ingredients from Chinese herbal 267 medicines being recognized as a potential strategy for treating COVID-19. Besides the small 268 molecules mentioned above, several other active ingredients from Chinese herbal medicines have 269 also been shown to exhibit potent anti-SARS-CoV-2 activities in vitro. Herba andrographitis (Chinese name: Chuanxinlian), composed of the whole plant or leaves 280 of Andrographis paniculata (Burm. F.) Nees, is a traditional herb that has been widely used over 281 many centuries to treat a range of diseases in China (Fig. 4A) Artemisinin, a first-line antimalarial drug, is a sesquiterpene that was first isolated in 1972 366 from the traditional Chinese medicine Artemisia annua L. by Xia (Fig. 4D ) (Xia et al., 2020a) . Rossetti, G., Gossen, J., Albani, S., Musiani, F., Herzog, K., Ye, Y., Giabbai, B., Demitri, N., 908 Jochmans, D., Jonghe, S.D., Rymenants, J., Summa, V., Tramontano, E., Beccari, A.R., 909 Leyssen, P., Storici, P., Neyts, J., Gribbon, P., Zaliani, A., 2020. Identification of inhibitors of 910 SARS-CoV-2 3CL-Pro enzymatic activity using a small molecule in-vitro repurposing screen. 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