key: cord-1054777-x032pcwx authors: Huang, Yu-Xi; Wang, Wen-Xiao; Zhang, Sai; Tang, Yu-Ping; Yue, Shi-Jun title: The database-based strategy may overstate the potential effects of traditional Chinese medicine against COVID-19 date: 2020-06-23 journal: Pharmacol Res DOI: 10.1016/j.phrs.2020.105046 sha: 66eb9fcf4c5544de57629afb2417dad0c01e98da doc_id: 1054777 cord_uid: x032pcwx nan The database-based strategy may overstate the potential effects of traditional Chinese medicine against COVID-19 Yu -Xi Huang 1 , Wen-Xiao Wang 1 The Coronavirus Disease 2019 (COVID-19) pandemic has become a huge threat to global health and developing an efficient therapeutic strategy will be of huge benefit [1] . Traditional Chinese medicine (TCM) plays an indispensable role in the prevention and treatment of several epidemic diseases with a long history. TCM scheme was also included in the Chinese guideline on diagnosis and treatment of COVID-19, and a number of clinical practices demonstrated that TCM exerts positive effects against COVID-19 through increasing the cure rate of western medicine, improving the aggravation and concomitant symptoms of COVID-19 [2] [3] . Generally, it is the active ingredients that contribute to the therapeutic effects of TCM on COVID-19, thus the deciphering of comprehensive information of active ingredients is in intense demand [4] [5] . Besides literature surveys and chemical methods, the natural product and traditional medicine databases seem to be a popular or efficient tool in the mechanistic investigation of TCM on Table 1 , each of them is flooded with massive information including TCM formulas, herbs, ingredients, targets, diseases, and the details under the corresponding items. Of note, some of them were built by data mining and manually collection from TCM classics, research articles, and E-library, while Table 1 , in which 73 of 80 articles were used TCMSP for further analysis, the following were ETCM (12 of 80) and TCMID (9 of 80), but none of them were updated earlier than November 2018. It was found that many studies have attempted to determine the anti-COVID-19 activity of ingredients from TCM solely by the binding ability of ingredients with angiotensin-converting enzyme 2 (ACE2) through molecular docking, since the increased expression of ACE2 were reported to facilitate infection with COVID-19 [6] . However, most of the active ingredients screened out in these studies are widely present in most Chinese herbs, such as quercetin (PubChem CID: 5280343), kaempferol (PubChem CID: 5280863), luteolin (PubChem CID: 5280445), rutin (PubChem CID: 5280805) and β-sitosterol (PubChem CID: 222284), etc., which seem not the characteristic compound and have yet to validate their anti-COVID-19 activities. Moreover, in these studies, the main focus is on constructing the interaction of herb-ingredient-target protein (Homo sapiens) to predict and analyze the effect of TCM against COVID-19, but it ignores whether these ingredients have a direct antiviral effect on SARS-coronavirus 2 (SARS-CoV-2). Subsequently, a total of 56 kinds of Chinese medicines (including Chinese patent medicine, TCM formula/decoction, herb pair, and single herb, etc.) were involved in these articles (Table S1) [1, 7] . Importantly, 36 kinds of Chinese medicines have not been validated experimentally or clinically in the treatment of COVID-19, indicating that databasebased strategy to repurpose these Chinese medicines for the clinical management of COVID-19 should be more cautious. Compared with Chinese patent medicines, these TCM formulas/decoctions consist of several or even dozens of herbs without corresponding quality criteria, which may pose a challenge to their quality control and database-based mechanistic investigations. In Chinese clinic, the combination of Chinese and Western medicines is still the mainstream for the treatment of COVID-19, so elucidating the exact role of these TCMs is in urgent demand and the database-based strategy will facilitate the mechanistic investigations of these clinically effective TCMs on COVID-19 to some extent. It is also worth noting that although ACE2 may be an ideal target for preventing COVID-19, we do not yet know whether it is safe to interfere with the normal operation of ACE2. Other receptors/targets of SARS-CoV-2 should also be explored to avoid research gridlock. Furthermore, the quality control and mechanistic investigations of TCM need to be strengthened so that TCM can be acceptable and beneficial for COVID-19 patients worldwide. Collectively, if the above issues are not solved in time, the abuse of databases will impede mechanistic investigations of TCM against COVID-19, but also may be counterproductive. The main characteristics of natural product and traditional medicine databases. Chemical Composition and Pharmacological Mechanism of Qingfei Paidu Decoction and Ma Xing Shi Gan Decoction Against Coronavirus Disease 2019 (COVID-19): In Silico and Experimental Study National Health Commission of the People's Republic of China.