key: cord-0698013-16vtdpmu authors: Ren, Wei; Liang, Pan; Ma, Yue; Sun, Qin; Pu, Qingrong; Dong, Li; Luo, Gang; Mazhar, Maryam; Liu, Jiali; Wang, Raoqiong; Yang, Sijin title: Research Progress of Traditional Chinese Medicine Against COVID-19 date: 2021-02-03 journal: Biomed Pharmacother DOI: 10.1016/j.biopha.2021.111310 sha: 6ff7d841adc13130a1144a5cf2349a690e0a0df9 doc_id: 698013 cord_uid: 16vtdpmu BACKGROUND: Currently, the number of confirmed cases and deaths of COVID-19 worldwide continues to rise, receiving great concern from the international community. However, there is no specific and widely accepted effective vaccines. The experience in controlling the outbreak in China has proven the effectiveness of traditional Chinese medicine (TCM). OBJECTIVES: This review aims to evaluate the role of TCM in COVID-19 treatment, hoping to provide references for prevention and control of global pandemic. DATA SOURCES: China National Knowledge Infrastructure, Web of Science, Baidu Scholar, ScienceDirect, Elsevier and PubMed were used to search literatures published from December 2019 to December 2020 by entering the keywords “Traditional Chinese medicine”, “COVID-19”, “Severe acute respiratory syndrome coronavirus 2”, “Pathogenesis”, “Syndrome differentiation”, “Prescriptions” and their combinations. Hence, we have performed an extensive review of research articles, reviews and primary scientific studies to identify TCM against COVID-19. RESULTS: Among clinical treatments of COVID-19, several TCM prescriptions and characteristic therapies have been effectively suggested, the underlying mechanisms of which are mainly involved in antiviral, anti-inflammatory, immunomodulatory and organ-protective effects of multi-components acting on multi-targets at multi-pathways. CONCLUSIONS: This review may provide meaningful and feasible information that can be considered for the treatment of COVID-19 pandemic globally. On March 11, 2020, the novel coronavirus disease 2019 (COVID-19) caused by a novel coronavirus (SARS-CoV-2), was declared as a global pandemic by World Health Organization (WHO) [1] . As of January 5, 2021, over 80 million confirmed cases have been reported across over 230 countries, areas, and territories, resulting in over 1.8 million deaths (according to data from WHO). The critical timeline in COVID-19 outbreak from December 2019 to December 2020 is shown in Figure. 1. The number of confirmed cases worldwide is still soaring. More than hundreds of preclinical studies and clinical trials have been conducted to search a way against COVID-19, however, there is no approved treatment for this widespread disease [2] . As the pandemic continues to escalate rapidly, it is urgent to discover safe and effective drugs or potential adjuvant treatments. Among them, traditional Chinese medicine (TCM) is utilized to effectively reduce symptoms of COVID-19 patients and inhibit disease progression from mild to severe, bringing remarkable clinical response [3] . It has been shown that over 70000 COVID-19 patients in China have received TCM treatment, with the total effective rate over 90% [4] . Here, we briefly review the characteristic, epidemiology J o u r n a l P r e -p r o o f and clinical features of SARS-CoV-2 infection, which may help to give a comprehensive understanding of this outbreak. Additionally, several prescriptions and characteristic therapies concluded from TCM in controlling COVID-19 are reviewed and analyzed. We also analyze the mechanisms of TCM prescriptions with multicomponents acting on multi-pathways and summarize the high frequency used herbs, the related components and signaling pathways, hoping to provide references for developing further anti-SARS-CoV-2 drugs to control the global outbreak. The comparison of SARS-CoV, MERS-CoV and SARS-CoV-2 are listed in Table. 1, including characteristics, epidemiology and TCM treatments. Similar to SARS-CoV and MARS-CoV, SARS-CoV-2 also belongs to a member of β coronavirus and single stranded RNA viruses, but its genome sequence is significantly distinct from those of SARS-CoV and MERS-CoV [5] . Several vital protein molecules encoded by these three coronavirus may be considered as possible targets for inhibiting viral infection and replication, including S protein, M protein, E protein, N protein, ACE2, 3CLpro, PLpro and RdRp [6] . Structural analysis showed that the receptor-binding domain of SARS-CoV-2 has approximately 10 times higher affinity to ACE2 than SARS-CoV [7] . The human-to-human transmission is mainly via respiratory droplets, contacts and aerosols [8, 9] . As the epidemic progresses, Wenling Wang et, al. reported that live SARS-CoV-2 is detected in human's feces, suggesting the possible existance of fecal transmission route [10] . During the asymptomatic period, it is also highly contagious with 44% transmission rate before symptoms appearing [11] . Reports showed that the consensus estimate for R0 value of SARS-CoV-2 is between 2 and 3, which is concluded from a mathematical model on the affected countries from the WHO situation published on 27 February, 2020 [12, 13] . All people are susceptible to these three coronaviruses, especially suffering from diseases like cardiovascular problems, diabetes and cancers [14] . SARS-CoV-2 has a tendency to attack elderly populations because of their higher ACE2 expression [15] . In terms of time distribution, SARS-CoV basically conforms to the epidemic of respiratory infectious diseases in winter and spring. Since 2014, the Note: "+" means positive index; "-" means negative index; "#" means some severe patients with no fever symptom; "↓" means decreasing index. Figure. 3) [29] . We also summarize the corresponding pathogenesis of SARS-CoV-2 infection from the perspective of western medicine, which is also shown in Figure 3 . Among them, in the mild stage, SARS-CoV-2 replication is occurred in the trachea, which may be incubated for 5-6 days [30] . After that, there is a mild symptom for 80% infected patients, mainly including fever and dry cough, which disappeared J o u r n a l P r e -p r o o f spontaneously within 6-10 days [8] . Nevertheless, about 20% patients developed viral infection from trachea to lungs [31] . SARS-CoV-2 binds with targets in alveolar epithelial cells such as ACE2 and TMPRSS2 and induces apoptosis response associated with vascular leakage [32] . This leakage causes the first wave of local inflammation and recruits immune cells from the blood into the lungs, thereby eliminating extracellular viruses and destroying infected cells [33] . The increased proinflammatory cytokines is attributed to the recruitment of leukocytes, further accelerating the local inflammatory response in lungs, including IL-6, IL-1β, IFN-γ, etc [34] . In this stage, the disease may rapidly develope into severe illness manifested as ARDS, acute lung injury, multiple organ dysfunction and septic shock [35] . More importantly, the detected levels of G-CSF, IP-10, MCP-1, MIP-1A and TNF-α in the serum of severe patients are higher than that of mild patients, implying a potential cytokine storm related to disease severity [19] . During the recovery stage, it is reported that lymphocyte count is also increased [36] . Besides, a declined number of natural killer T cell (NKT) is observed in patients in this stage, suggesting that the presence of these cells may be used to clear the virus during the initial infection [36] . Some patients still have clinical manifestations such as cough, fatigue, poor appetite, abnormal mood, which needs more time to recovery completely [37] . Taken together, we can acquire a comprehensive understanding of pathogenesis of COVID-19 from both TCM and western medicine, which is contributed to find the optimal treatment in clinic. Further, J o u r n a l P r e -p r o o f TCM has shown obvious effects on treatment of COVID-19, having a preventive role in mild patients, improving the prognosis of severe patients, and reducing the mortality rate [39] . Currently, this disease is divided into five stages on the basis of different severity: mild stage, moderate stage, severe stage, critical stage and recovery stage. Here, we summarize the herbal composition, active compounds, potential mechanisms and clinical applications of representative TCM prescriptions for the treatment of COVID-19, which is detailly listed in Table. 3. These prescriptions with multicompounds exhibit different pharmacologic actions on treating COVID-19 via multitargets and multi-pathways, acquiring satisfactory clinical efficacy. lung-heat and relieve asthma, pungent-cool and ventilate lung. This prescription is applicable to reduce cough and asthma caused by evil heat obstructed in the lung, which is mostly used to treat patients with external wind-cold, or wind-heat invading the lungs and internal heat and external cold [62] . Previous reports revealed that MXSGD J o u r n a l P r e -p r o o f exhibits antiviral effects via inhibiting viral proliferation and absorption, and protecting infected cells, which are more effective than ribavirin [63] . Furthermore, MXSGD has shown obvious improvement on H1N1-induced acute lung injury in mice model, by decreasing lung cell apoptosis and reducing TNF-α concentration in serum [64] . Shiying Zhang et, al. found that MXSGD can control disease progression by regulating multiple targets, including AKT1, MAPK3, IL-6, TP53, TNF, CASP3, EGFR and MAPK1, which interacted with ACE2 that closely related to disease development [40] . Animal experiments have confirmed that the anti-inflammatory effects of MXSGD are mediated via thrombin and Toll-like receptor signaling pathway [62] . The network analysis also showed that the predicated five active compounds including quercetin, kaempferol, isorhamnetin, naringenin and wogonin are effective in inhibiting SARS-CoV-2 replication and reducing cytokine storm [42, 65] . According to analysis of clinical medication of 225 patients with COVID-19 in Wanzhou, Chongqing city, it is found that intervention therapy with TCM is about 87% (n = 195 cases), 20.29% of which is attributed to MXSGD [66] . Additionally, after the combined application of conventional western medicine and MXSGD in 40 common cases for 7 d, the disappearance rates of fever, fatigue and cough are 96.8%, 100% and 81.8%, respectively. The levels of IL-6 and CRP in serum are significantly decreased, reflecting a weakened inflammation [41] . Based on both network pharmacology and bioinformatics technology analysis, researchers speculate that MXSGD blocks the conversion of patients with COVID-19 from mild to severe stage by inhibiting cytokine storm [67] . Experimental studies have shown that DYD has obvious antipyretic effects, the mechanism of which is related to decreasing prostaglandin E2 level in the cerebrospinal fluid, thereby reducing the excitatory stimulation to the body temperature center [74] . During January to April, 2003, a total of 112 confirmed SARS cases were treated with DYD, with over 93.7% of the patients experiencing noticeable symptoms reduction and recovery [73] . This prescription is quite consistent with the treatment principle for COVID-19 in terms of etiology, pathogenesis, efficacy and indications, thus being used for mild and common cases during the clinical treatment period. In clinic, it is found that DYD can relieve symptoms of cough, asthma and dry throat, improve prognosis of J o u r n a l P r e -p r o o f COVID-19 patients, and shorten disease progression, making it worthy of clinical application and promotion [46, 75] . In the treatment of COVID-19, DYD also decreases the severity of ARDS by acting on cytokine storm [73] . Furthermore, by using network pharmacology and molecular docking method, Yang Zong et, al. found that active compounds in DYD prescription may act on PTGS2, IL-6, IL-1β, CCL2 and other targets by combining with ACE2 to regulate multiple signaling pathways, having a therapeutic effect on COVID-19 [47] . Xiaofeng Ruan reported that there was a high affinity between the key compounds (kaempferol, quercetin, naringenin and formononetin) and key targets (IL-6, IL-1β, CCL2) through molecular docking analysis. Finally, DYD was demonstrated to reduce the level of IL-6 in COVID-19 patients, exerting anti-inflammatory and immune regulation activities [26] . Huashi The main herbs in Shufeng Jiedu (SFJD) formula are Reynoutria japonica Houtt, Lianhua Qingwen (LHQW) has been widely concerned and recognized for its unique theoretical composition and previous remarkable efficacy in combating SARS and influenza epidemics, becoming a representative Chinese patent medicine for public health events in the respiratory system [86, 87] . This prescription is composed of J o u r n a l P r e -p r o o f management because of its property of heat-clearing and lung-freeing, and multifunctionality in coping with virus infection and inflammatory response [88] . replication in Vero E6 cells and reduce generation of pro-inflammatory cytokines such as IL-6, TNF-α, CCL-2/MCP-1 and CXCL-10/IP-10, helping to protect from viral infection [89] . hydroxyphenyl)chroman-4-one) in HXZQ, which is better than that of remdesivir, implying anti-SARS-CoV-2 activity by directly inhibiting virus replication [98] . Network pharmacology preliminarily predicted that this process may be affected via PI3K-Akt signaling pathway. Besides, quercetin, isorhamnetin and pueraria aglycone in HXZQ have the strongest binding affinity to ACE2, and act on targets such as PTGS2, HSP90AB1, AR and CAMSAP2 to regulate multiple signal pathways [55] . Cytokine storm has been confirmed in severe COVID-19 patients, especially the existence of IL-6 [99] . HXZQ has an obvious anti-inflammatory effects, including decreasing levels of various pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, IL-2) and increasing level of IL-10 as well as regulating NF-κB pathways, indicating that HXZQ may have therapeutical effects for COVID-19 patients [100] . Clinically, HXZQ combined with western medicine significantly reduced clinical symptoms (fever, cough, fatigue, white and greasy tongue fur) in 11 confirmed cases with lung stagnation, prevented the transition from mild to severe, and increased the clinical cure rate, which is worthy of popularization and application [56] . Jinhua Qinggan (JHQG) granule with functions of heat-clearing and detoxification, Most of the patients found in Guangzhou, China had symptoms of lung-heat in the early J o u r n a l P r e -p r o o f stage, accumulation of damp and heat in the middle stage, and lack of Yin-qi in the later stage [110] . Above herbs and their combinations illustrated that the principles of TCM are strengthening resistance and eliminating pathogenic factors to achieve the treatment of both symptoms and root causes [112] . Yufeng Huang et, al. summarized that the active compounds and possible mechanisms from several TCM prescriptions researches. Among them, quercetin, kaempferol, luteolin, isorhamnetin, baicalein, naringenin, wogonin, ergosterol, lonicerin and tussilagone are considered as the top ten active compounds. AEC2 and 3CL proteins may be two direct targets for the inhibition of SARS-CoV-2 replication [4] . Boyu Pan et, al. reported that quercetin not only has a receptor blocking effect, but also has a virus-neutralizing effect on SARS-CoV-2, suggesting a promising candidate against COVID-19 [113] . Additionally, the top ten targets such as COX-2, CASP3, IL-6, MAPK1, EGFR, IL-2, TNF and CCL-2 are closely linked to the top ten signaling pathway of IL-17, HIF-1, NF-κB, Ras, TNF, MAPK, PI3K-Akt, Toll-like receptor and Th17 cell differentiation [4] . The detailed herbal combination, active compounds and mechanisms are illustrated in Table. 4. Therefore, the mechanism of TCM prescriptions to treat COVID-19 is mainly involved in antiviral, anti-inflammatory, immunomodulatory and organ-protective effects of multi-components acting on multi-pathways. Future research can focus on above compounds, targets and signaling pathways to further develop anti-SARS-CoV-2 drugs. J o u r n a l P r e -p r o o f Currently, because of the long time to develop vaccines, it is particularly important to prevent viral infection and improve body immunity. The Preventive treatment of disease concept from TCM theory has unique advantages in the practical application of COVID-19, including moxibustion, TCM aromatherapy, TCM functional exercise, food therapy, TCM tea replacement and TCM foot bath [114] . Here, as illustrated in deficiency combined with CFS, which may alleviate symptoms and regulate the body's immune system [116] . Ping Liu et, al. reported that moxibustion could increase the total number of T cells [117] . In COVID-19 therapy, moxibustion has functions of antiinflammatory, antiviral, and immune response adjustment, which has been applied in SARS infection [118] . Xianbao Huang et, al. found that heat-sensitive moxibustion used as adjuvant treatment can effectively relieve symptoms of COVID-19 (n = 42), including chest oppression, poor appetite and lassitude, negative emotions [119] . As shown in Table. 5 Besides, the use of TCM aromatherapy has a long history for epidemic prevention, mainly including TCM sachets and TCM aroma. During COVID-19 outbreak, this special therapy is widely applied among seven provinces and one city, helping to prevent viral infection and improve immunity. For example, a prescription of TCM sachet suggested by the government of Heilongjiang, China, is mainly composed of Pogostemon cablin, Eupatorium fortune, Cinnamomum camphora, Realgar, Angelica dahurica, Artemisia argyi [120] . Above herbs are made in bulk, packed into compact bags and carried every day, which is effective in strengthening the body resistance, resolving dampness and repelling foulness. Besides, several herbs are decocted to fumigate the whole body, including Perilla frutescens, Artemisia argyi, Acorus tatarinowii, ValerianajatamansiJones, Mentha haplocalyx, etc. Aromatherapy herbs are acted on the mouth and nose, the Xuanfu and the meridians to prevent and treat diseases, having functions of anti-inflammatory, anti-allergic, promoting metabolism, enhancing immunity [121] . However, the anti-epidemic effect and mechanism of TCM aromatherapy for different physiques still need to be thoroughly and systematically studied. The core concept of TCM functional exercise is adjusting the functions of viscera and channels and enriching the essence-qi to achieve the purpose of prevention and rehabilitation [122] . Compared with modern functional exercise, it emphasizes the J o u r n a l P r e -p r o o f combination of movement and static, preventing illness before occurring, and preventing recovery after illness [123] . TCM functional exercise has difficulty to directly treat COVID-19, or cut off the transmission path, however, many studies showed that TCM functional exercise has received satisfactory clinical response on the basis of conventional treatment, which can effectively improve the patient's cardiopulmonary function, increase immunity, correct negative emotions and accelerate rehabilitation. Importantly, there is also a positive effect for elderly patients with previous underlying diseases to keep healthy [124] . Lulu Zha et, al. reported that a lower remission rate in productive cough and expectoration was observed after modified Eight-Section Brocade among 60 mild cases with a median age of 54 years old, confirming the adjuvant therapeutic effect of TCM functional exercise in mild patients [125] . Moreover, for mild and common patients with dry cough and fever, Eight-Section Brocade combined with Six-character formula is recommended to enhance the function of lung, spleen and stomach, with a practice of twice a day and six times per style. During the recovery stage, this combined exercise is focused on promoting healthy Qi. Besides, Eight-Section Brocade and Five-animal exercises may help severe patients to recover lung function and relieve negative emotions such as fear, anxiety and depression [126] . Yu Shi et, al. proved that Tai Chi is effective and safe for COVID-19 in recovery period via meta-analysis [127] . Actually, it is also suitable for mild, common and severe cases to improve lung function. Furthermore, food therapy, TCM tea replacement and TCM foot bath are also considered as the non-drug treatment aimed at population with different body to replenish and restore lung-qi, strengthen the spleen and stomach, helping to prevent and recovery from infection, which is detailly listed in Table. 5 [123] . On February 24, the Chinese method in the treatment of COVID-19 was recognized by Bruce Elwald, a senior adviser to the director general of WHO [128] . In TCM theory, COVID-19 is a highly pathogenic cold-dampness disease and evil Qi in this disease plays the leading role in the disease at this time, causing fever and dry cough after entering into lung guard. TCM therapy emphasizes the holistic view and syndrome differentiation, following the basic principle of strengthening the body and eliminating evils before identifying pathogen. It is difficult and delayed to find targeted and effective drugs against COVID-19 from modern medicine. Another advantage of TCM for COVID-19 treatment is the lower relapse rate than that of western medicine. Statistically, the total relapse rate is approximately 0.1% of 8,000 cases. To date, there is no relapse cases occurred in many hospitals [128] . Previous mentioned TCM prescriptions and characteristic therapies mainly focus on resolving phlegm and relieving cough, clearing away heat and eliminating dampness, which help to enhance vital Qi and improve immunity. Nannan Shi et, al. conducted a non-randomised controlled trial to confirm superiority of a combination of HSBD and TCM injection to treat COVID-19 [129] . Yuanyuan Wang et, al. summarized a single-center, retrospective study on patients with severe COVID-19 and found that the use of TCM granules reduced the 28-day mortality rate and the time to fever alleviation [130] . Extensive data have shown to support the therapeutic effects of TCM treatment, however, there are no Prospective role of thyroid disorders in monitoring COVID-19 pandemic Current Prevention of COVID-19: Natural Products and Herbal Medicine Research progress and challenges to coronavirus vaccine development Review on the potential action mechanisms of Chinese medicines in treating Coronavirus Disease 2019 (COVID-19) Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan Traditional Chinese medicine herbal extracts of Cibotium barometz, Gentiana scabra, Dioscorea batatas, Cassia tora, and Taxillus chinensis inhibit SARS-CoV replication Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia Droplets and Aerosols in the Transmission of SARS-CoV-2 Detection of SARS-CoV-2 in Different Types of Clinical Specimens Anti-COVID-19 drug screening: Frontier concepts and core technologies Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding Presumed Asymptomatic Carrier Transmission of COVID-19 Treatment and prognosis of COVID-19: Current scenario and prospects (Review) Different longitudinal patterns of nucleic acid and serology testing results based on disease severity of COVID-19 patients Clinical features of patients infected with 2019 novel coronavirus in Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Prevention and control strategies of COVID-19 based on theory of principle, method and prescription of Treatise on Febrile Diseases Preventive treatment of disease in dietetic therapy based on Qianjin Fang Discussion on SUN Si-miao's contribution to acupuncture and moxibustion medicine Current Situation and Thinking on Traditional Chinese Medicine Prevention and Treatment of Acute Viral Respiratory Tract Infections Diseases Study on the molecular mechanism of Sanxiao decoction in the treatment of novel coronavirus pneumonia Mechanism of Dayuanyin in the treatment of coronavirus disease 2019 based on network pharmacology and molecular docking Analysis of the etiology and pathogenesis of new coronavirus pneumonia from "Cold and Dampness Treatment Discussions on the prevention treatment of COVID-19 based on the classic theories of traditional Chinese medicine Discussion on Thoughts for Treatment of Coronavirus Disease 2019 Based on Cold-damp Epidemics Virological assessment of hospitalized patients with COVID-2019 SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract ACE2, TMPRSS2 distribution and extrapulmonary organ injury in patients with COVID-19 COVID-19 infection: the perspectives on immune responses Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19 Immunity, endothelial injury and complement-induced coagulopathy in COVID-19 COVID-19: The Emerging Immunopathological Determinants for Recovery or Death, Front Microbiol Three Cases of Using Method of Strengthening Healthy Qi, Expelling Pathogens and Dredging Collaterals in the Convalescence of COVID-19 Study on the Mechanism of Traditional Chinese Medicine with Different Regulations in Coronary Pneumonia 2019(COVID-19) Based on Network Pharmacology Herbal medicine for treatment of children diagnosed with COVID-19: A review of guidelines Systematic Pharmacological Strategies to Explore the Regulatory Mechanism of Ma Xing Shi Gan Decoction on COVID-19 Forty cases of common COVID-19 treated with modified Maxing Shigan Decoction combined with western medicine routine treatment Study on the mechanism of add or subtract Maxing Shigan decoction in the treatment of the severe novel coronavirus pneumonia based on network pharmacology Clinical observation of Qingfeipaidu Decoction in the Treatment of COVID-19 Mechanism of Qingfei Paidu decoction for treatment of COVID-19: analysis based on network pharmacology and molecular docking technology Network pharmacology-based study on material basis and mechanism of Qingfei Paidu Decoction against Novel coronavirus pneumonia Two cases of treatment of COVID-19 by adding or subtracting Da Yuan Decoction Exploring active compounds of Da-Yuan-Yin in treatment of COVID-19 based on network pharmacology and molecular docking method Pharmacological mechanism and network pharmacology research of Huashibaidu formula in treating COVID-19 Material basis research of Anti-COVID-19 Huashibaidu granule gormula Investigation on mechanism and active components of Shufeng Jiedu Capsule in treatment of COVID-19 based on network pharmacology and molecular docking The value analysis of Shufeng Jiedu capsule combined with Abidor in the treatment of mild COVID-19 Shufeng Jiedu, a promising herbal therapy for moderate COVID-19: Antiviral and anti-inflammatory properties, pathways of bioactive compounds, and a clinical real-world pragmatic study Clinical Effectiveness and Case Analysis in 54 NCP Patients Treated with Lanhuaqingwen Granules Study on the network pharmacology and preliminary evidence of Lianhua Qingwen in the treatment of novel coronavirus (2019-nCoV) pneumonia Study on active compounds from Huoxiang Zhengqi Oral Liquid for prevention of coronavirus disease 2019 (COVID-19) based on network pharmacology and molecular docking Huoxiang Zhengqi Powder combined with western medicine in the treatment of 11 COVID-19 cases Study on the network pharmacology of Jinhua Qinggan Granules in the treatment of COVID-19 Clinical Observation on Jinhua Qinggan Granule Combined with Conventional Western Medicine Therapy in Treating Mild Cases of Coronavirus Disease Clinical study on 37 case of COVID-19 treated with integrated traditional Chinese and western medicine A systematic pharmacological investigation of pharmacologically active ingredients in Toujie Quwen granules for treatment of COVID-19 Network pharmacology, molecular docking integrated surface plasmon resonance technology reveals the mechanism of Toujie Quwen Granules against coronavirus disease 2019 pneumonia 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 Experimental study on effect of Maxingshigan Decoction on antiinfluenza virus in vitro Effect of Maxing Shigan Tang on H1N1 Influenza A Virus-Associated Acute Lung Injury in Mice The Curative Mechanism of Maxing Shigan Decoction on Cytokine Storm of COVID-19 Based on Network Pharmacology The Clinical Characteristics and Medication Analysis of Corona Virus Disease The curative mechanism of Maxingshigan Decoction on cytokine storm of COVID-19 pneumonia based on network pharmacology Research progress of the mechanism of anti-COVID-19 drugs Effect of self-developed Fuzhengbixie formula and Qingfeipaidu Mixture on the prevention and treatment of the coronavirus disease Clinical characteristics of 22 cases of COVID-19 and analysis of the combination of Chinese and Western Medicine Investigating mechanism of Qing-Fei-Pai-Du-Tang for treatment of COVID-19 by network pharmacology Protection against COVID-19 injury by qingfei paidu decoction via anti-viral, antiinflammatory activity and metabolic programming The Important Role of Volatile Components From a Antifebrile effect of Dayuanyin and its determination by Treating one elderly patient with severe COVID-19 from the angle of treating damp-warm disease Experience summary and suggestion on diagnosis and treatment program of traditional Chinese medicine treating severe type coronavirus disease 2019 The therapeutic efficacy of Huashi Baidu Formula combined with antiviral drugs in the treatment of COVID-19: A protocol for systematic review and meta-analysis Study on novel coronavirus pneumonia (COVID-19) mechanism by Huashi Baidu Formula based on network pharmacology Characteristics of registered clinical trials on traditional Chinese medicine for coronavirus disease 2019 (COVID-19): a scoping review Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Huashi Baidu formula in the treatment of COVID-19 Clinical Effect of Shufeng Jiedu Capsules for Acute Upper Respiratory Tract Infection and Its Effect on Inflammatory Factors Discussion of Shufeng Jiedu Capsule Treating COVID-19 Clinical evaluation of Shufeng Jiedu Capsules combined with umifenovir (Arbidol) in the treatment of common-type COVID-19: a retrospective study Mechanism of Shufeng Jiedu Capsule in the treatment of novel coronavirus pneumonia based on network pharmacology and molecular docking Investigating the mechanism of ShuFeng JieDu capsule for the treatment of novel Coronavirus pneumonia (COVID-19) based on network pharmacology Natural herbal medicine Lianhuaqingwen capsule anti-influenza A (H1N1) trial: a randomized, double blind, positive controlled clinical trial Inhibitory effects of three prescriptions of traditional Chinese medicine on SARS-associated coronavirus in vitro Similarity and Specificity of Traditional Chinese Medicine Formulas for Management of Coronavirus Disease 2019 and Rheumatoid Arthritis Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2) Clinical Effectiveness and Case Analysis in 54 NCP Patients Treated with Lanhuaqingwen Granules Clinical observation on the treatment of 63 suspected cases of novel coronavirus pneumonia with traditional Chinese medicine Lianhua Qingwen Efficacy and safety of Lianhuaqingwen capsules, a repurposed Chinese herb COVID-19: Clinical aspects and therapeutics responses Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening Clinical Efficacy of Lianhua Qingwen Granules and its Mechanism on COVID-19 Based on Network Pharmacology Analysis on Chinese medical clinical characteristics of 50 patients with novel coronavirus-infected pneumonia Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro Preliminary study on the effective components and mechanism of Huoxiang Zhengqi decoction in Inhibiting the replication of novel coronavirus The role of Interleukin 6 inhibitors in therapy of severe COVID-19 Research progress on potential application of Huoxiang Zhengqi in prevention and treatment of coronavirus disease Research Progress on the Anti-virus Effect of Lonicerae Flos Effect of Scutellariae Radix on expression of inflammatory cytokine protein and gene in lung of mice with viral pneumonia caused by influenza virus FM1 infection Clinical efficacy of different doses of Jinhuaqinggan granule on influenza and serum levels of cytokines, Modern medicine Treating Influenza Patients of Wind-Heat Affecting Fei Syndrome by Jinhua Qinggan Granule: a double blinded Randomized Control Trial Effect of Jinhua Qinggan granules on novel coronavirus pneumonia in patients Efficacy and safety of Jinhua Qinggan granules for coronavirus disease 2019 (COVID-19): A protocol of a systematic review and meta-analysis Discussion on the Mechanism of Jinhua Qinggan Granule in the Treatment of Novel Coronavirus Pneumonia Clinical efficacy of different doses of Jinhuaqinggan granule on influenza and serum levels of cytokines Study on the active compounts in the adjuvant treatment of novel coronavirus pneumonia (COVID-19) with Jinhua Qinggan Granules based on network pharmacology and molecular docking Interpretation of Trial Scheme for Traditional Chinese Medicine in Prevention and Treatment of Novel Coronavirus Pneumonia in Guangdong Province and Experts'Medical Case Analysis 2 cases reports of corona virus disease 2019 treated by ToujieQuwen granules Analysis of medication characteristics of traditional Chinese medicine in treating COVID-19 based on data mining Chinese herbal compounds against SARS-CoV-2: Puerarin and quercetin impair the binding of viral S-protein to ACE2 receptor The role played by traditional Chinese medicine in preventing and treating COVID-19 in China Discussion on the prevention and treatment of seasonal epidemic diseases by moxibustion Clinical Study on Effect of Moxibustion Treating Hepatitis B Virus Patients Combine Chronic Fatigue Syndrome Clinical study of point injection combined with moxibustion in the treatment of leukopenia after chemotherapy Nine cases of the chronic stage of SARS treated by moxibustion 42 cases of coronavirus disease 2019 of the ordinary type with the adjuvant treatment of heat-sensitive moxibustion 42 The application of influenza scents in the prevention of COVID-19, China's Naturopathy A Study on the Application of TCM Aromatherapy in Covid-19 Prevention and Treatment Based on Constitutionology Theory Research on four kinds of technological evolution of health Qigong An Overall Analysis of Non-drug Intervention Programs for COVID-19 Application of eight-section brocade in postoperative rehabilitation of non-small cell lung cancer patients, Chinese nursing research Modified rehabilitation exercises for mild cases of COVID-19 Discussion on the Application of Traditional Chinese Medicine Functional Exercise in Prevention and Rehabilitation of COVID-19 Based on the Thought of "Preventive Treatment of Disease Chi for coronavirus disease 2019 in recovery period: A protocol for systematic review and meta analysis Prevention and treatment of COVID-19 using Traditional Chinese Medicine: A review Efficacy and safety of Chinese herbal medicine versus Lopinavir Effect and safety of Chinese herbal medicine granules in patients with severe coronavirus disease 2019 in Wuhan, China: a retrospective, single-center study with propensity score matching Figure. 1. The critical timeline in COVID-19 outbreak from The authors declare that there are no conflicts of interest.