Herbal medicines exhibit a high affinity for ACE2 in treating COVID-19.

Coronavirus Disease 2019 (COVID-19) has been an unprecedented disaster for people around the world. A point particularly worth noting is that herbal medicines have made great contributions to the prevention and treatment of COVID-19 in China. Angiotensin converting enzyme 2 (ACE2) has been identified as the critical functional receptor for SARS-CoV-2. It can bind to the receptor-binding domain (RBD) of the spike protein (S protein), which is responsible for the entry of the coronavirus into host cells. Therefore, ACE2 can be regarded as an important intervention target for COVID-19. Recently, many herbal medicines have exhibited a high affinity for ACE2 in treating COVID-19. The current work summarized these herbal medicines including formulas (such as Lianhua Qingwen capsules, Xuebijing injection, Qingfei Paidu Decoction, Huashi Baidu formula, Shufeng Jiedu capsules, and Maxing Shigan decoction), single herbs including Ephedra sinica Stapf (Mahuang), Scutellariae radix (Huangqin), Lonicera japonica (Jinyinhua), and Houttuynia cordata (Yuxingcao), and active ingredients (such as ursodeoxycholic acid, glycyrrhizic acid, glycyrrhizin, salvianolic acid, quercetin, and andrographidine C), which have exhibited a high affinity for ACE2 in treating COVID-19. We hope this work may provide meaningful and useful information on further research to investigate the mechanisms of herbal medicines against SARS-CoV-2 and follow-up drug discovery.

Traditional Chinese medicine as an adjunctive therapy for mild and common COVID-19: A systematic review and network meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) in many countries is still very serious. At present, there is no specific and effective drug for this disease. Traditional Chinese medicine (TCM) has played a great role in fighting against COVID-19. However, their effectiveness and safety are still obscure and deserve further investigation. The aim of the study was to evaluate the efficacy and safety of TCM assisted in conventional treatment in the treatment of mild and common COVID-19. METHODS: PubMed, EMbase, MEDLINE, China National Knowledge Infrastructure Database, WANFANG DATA, and VIP Chinese Science and Technology Periodical Database were searched for randomized controlled trials (RCTs) and non-randomized controlled trials of TCM assisted in conventional treatment. The RCT research quality was evaluated by Cochrane 5.1.0 bias risk scale and the non-randomized controlled trial research quality was evaluated by Newcastle Ottawa scale, and the statistical analysis was conducted by Revman 5.3 and R software. The bias and sensitivity of the statistical results were analyzed by STATA 14.0. Registration number: CRD42020210619. RESULTS: Fifteen studies were included with 7 RCT studies and 8 retrospective cohort studies, involving a total of 1623 patients. Compared with the control group, TCM can improve the main index clinical effective rate (odds ratio [OR] = 2.64, 95% Confidence interval (CI) [1.94,3.59], P < .00001). The results of Begg test (Pr > z = 0.266) and sensitivity analysis showed that the results were relatively stable. Toujie Quwen (OR = 4.9, 95%CI [1.9,14.0]), Shufeng Jiedu (OR = 2.9, 95%CI [1.5,5.7]), and Lianhua Qingwen (OR = 2.4, 95%CI [1.6,3.6]) were with the best. It can also improve the main clinical symptoms (fever, cough, fatigue, and the regression time of the 3 symptoms), severe conversion rate, and computed tomography improvement rate. Its safety was not significantly compared with conventional treatment. However, in terms of safety of a single TCM, Shufeng Jiedu (OR = -0.86, 95%CI [-1.89,0.09]) and Lianhua Qingwen (OR = -0.49, 95%CI[-0.94,-0.05]) were lower than those of conventional treatment. CONCLUSION: TCM as an adjuvant therapy combined with conventional treatment has good curative effect on mild and common type of COVID-19 patients. Its advantages lie in clinical efficacy and improvement of symptom group, and can prevent patients from transforming to severe disease. In terms of clinical efficacy and safety, Shufeng Jiedu and Lianhua Qingwen have obvious advantages, which are worthy of clinical promotion.

Treating patients infected with the SARS-CoV-2 Omicron variant with a traditional Chinese medicine, Shufeng Jiedu capsule.

Patients infected with the Omicron variant of SARS-CoV-2 mainly develop mild COVID-19, manifesting as upper respiratory symptoms, fatigue, and fever. Shufeng Jiedu capsule (SFJDC), a traditional Chinese medicine indicated for treatment of upper respiratory infections in China, was tested for its efficacy and safety in treatment of an Omicron infection at a mobile cabin hospital in response to an outbreak of COVID-19 in Shanghai, China in April 2022. In this open-label, randomized controlled trial, patients in the control group received best supportive care, while those in the test group received additional SFJDC therapy for 7 days. SFJDC markedly alleviated patients' symptoms including a sore throat, coughing, fatigue, and a fever after 7 days of treatment. The virus negative time was significantly shorter in the SFJDC treatment group, but there were no obvious differences in the virus negative rate between the two groups at the end of the 7-day follow-up. These results suggest that patients with the Omicron infection may benefit from SFJDC treatment. Double-blind, randomized controlled trials are warranted to comprehensively evaluate the efficacy and safety of SFJDC in a large cohort study in the future.

[Meta analysis on the treatment of coronavirus disease 2019 by traditional Chinese and Western medicine].

OBJECTIVE: To evaluate the clinical efficacy and safety of combination of traditional Chinese and Western medicine in the treatment of coronavirus disease 2019 (COVID-19) by Meta analysis. METHODS: The clinical randomized controlled trials (RCT) and cohort studies on the treatment of COVID-19 with combination of Chinese traditional and Western medicine published on CNKI, Wanfang database, VIP database and PubMed were searched by computer from January 2020 to June 2020. Patients in the simple Western medicine treatment group were treated with routine treatment of Western medicine, and the patients in integrated traditional Chinese and Western medicine treatment group were treated with traditional Chinese medicine on the basis of routine treatment of Western medicine. The main outcome was the total effective rate of treatment. The secondary outcome were the antipyretic rate, chest CT recovery rate, lymphocyte count (LYM), C-reactive protein (CRP) level and safety. The Cochrane manual and the Newcastle Ottawa Scale (NOS) were used to evaluate the quality of the literature; the RevMan5.3 software was used to analyze the articles that meets the quality standards, and a funnel chart was drawn to evaluate the total effective publication bias. RESULTS: Thirteen articles were analyzed, including 1 039 COVID-19 patients, 559 in integrated traditional Chinese and Western medicine treatment group and 480 in simple Western medicine treatment group. The results of Meta- analysis showed that compared with the simple Western medicine treatment group, the combination of routine treatment of Western medicine and traditional Chinese medicine Qingfei Paidu decoction, Lianhua Qingwen granule, Shufeng jiedu capsule, Xuebijing injection or Reyanning mixture could significantly improve the total effective rate, antipyretic rate and chest CT recovery rate [total effective rate: odds ratio (OR) = 2.95, 95% confidence interval (95%CI) was 2.10-4.14, P < 0.000 01; antipyretic rate: OR =3.01, 95%CI was 1.64-5.53, P = 0.000 4; chest CT recovery rate: OR = 2.53, 95%CI was 1.83-3.51, P = 0.000 1], increase LYM levels [mean difference (MD) = 0.26, 95%CI was 0.02-0.50, P = 0.03], and reduce of CRP content (MD = -17.68, 95%CI was -33.14 to -2.22, P = 0.02). Based on the funnel chart analysis of 12 articles with total efficiency, the result showed that the funnel chart distribution was not completely symmetrical, indicating that there might be publication bias. CONCLUSIONS: On the basis of routine treatment with Western medicine, combined with traditional Chinese medicine can significantly improve the total effective rate of COVID-19 and improve the laboratory results and clinical symptoms of patients. Compared with the routine treatment of Western medicine alone, the combination of traditional Chinese and Western medicine has better clinical efficacy and safety.

Efficacy and Safety of Integrated Traditional Chinese and Western Medicine for Corona Virus Disease 2019 (COVID-19): a systematic review and meta-analysis.

Corona virus disease (COVID-19) has now spread to all parts of the world and almost all countries are battling against it. This study aimed to assess the efficacy and safety of Integrated Traditional Chinese and Western Medicine (Hereinafter referred to as "Integrated Medicine") to COVID-19. We searched six major Chinese and English databases to identify randomized controlled trials (RCTs) and case-control studies (CCSs) of Integrated Medicine on COVID-19. Two reviewers independently screened, identified studies, and extracted data. Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale were used to assess the quality of included RCTs and CCSs, respectively. Stata (version 13.0; StataCorp) was used to perform meta-analyses with the random-effects model. Risk ratio (RR) was used for dichotomous data while the weighted mean difference (WMD) was adopted for continuous variables as effect size, both of which were demonstrated in effect size and 95% confidence intervals (CI). A total of 11 studies were included. Four were RCTs and seven were CCSs. The sample size of including studies ranged from 42 to 200 (total 982). The traditional Chinese medicine included Chinese medicine compound drugs (QingFei TouXie FuZhengFang) and Chinese patent medicine (e.g. Shufeng Jiedu Capsule, Lianhua Qingwen granules). Compared with the control group, the overall response rate [RR = 1.230, 95%CI (1.113, 1.359), P = 0.000], cure rate [RR = 1.604, 95%CI (1.181, 2.177), P = 0.002], severity illness rate [RR = 0.350, 95%CI (0.154, 0.792), P = 0.012], and hospital stay [WMD = -1.991, 95%CI (-3.278, -0.703), P = 0.002] of the intervention group were better. In addition, Integrated Medicine can improve the disappearance rate of fever, cough, expectoration, fatigue, chest tightness and anorexia and reduce patients' fever, and fatigue time (P < 0.05). This review found that Integrated Medicine had better effects and did not increase adverse drug reactions for COVID-19. More high-quality RCTs are needed in the future.

Potential Role of Gut Microbiota in Traditional Chinese Medicine against COVID-19.

The coronavirus disease 2019 (COVID-19) spreads and rages around the world and threatens human life. It is disappointing that there are no specific drugs until now. The combination of traditional Chinese medicine (TCM) and western medication seems to be the current more effective treatment strategy for COVID-19 patients in China. In this review, we mainly discussed the relationship between COVID-19 and gut microbiota (GM), as well as the possible impact of TCM combined with western medication on GM in the treatment of COVID-19 patients, aiming to provide references for the possible role of GM in TCM against COVID-19. The available data suggest that GM dysbiosis did occur in COVID-19 patients, and the intervention of GM could ameliorate the clinical condition of COVID-19 patients. In addition, TCMs (e.g., Jinhua Qinggan granule, Lianhua Qingwen capsule, Qingfei Paidu decoction, Shufeng Jiedu capsule, Qingjin Jianghuo decoction, Toujie Quwen granules, and MaxingShigan) have been proven to be safe and effective for the treatment of COVID-19 in Chinese clinic. Among them, Ephedra sinica, Glycyrrhiza uralensis, Bupleurum chinense, Lonicera japonica,Scutellaria baicalensi, and Astragalus membranaceus are common herbs and have a certain regulation on GM, immunity, and angiotensin converting enzyme 2 (ACE2). Notably, Qingfei Paidu decoction and MaxingShigan have been demonstrated to modulate GM. Finally, the hypothesis of GM-mediated TCM treatment of COVID-19 is proposed, and more clinical trials and basic experiments need to be initiated to confirm this hypothesis.

Investigating the mechanism of ShuFeng JieDu capsule for the treatment of novel Coronavirus pneumonia (COVID-19) based on network pharmacology.

ShuFeng JieDu capsule (SFJDC), a traditional Chinese medicine, has been recommended for the treatment of COVID-19 infections. However, the pharmacological mechanism of SFJDC still remains vague to date. The active ingredients and their target genes of SFJDC were collected from TCMSP. COVID-19 is a type of Novel Coronavirus Pneumonia (NCP). NCP-related target genes were collected from GeneCards database. The ingredients-targets network of SFJDC and PPI networks were constructed. The candidate genes were screened by Venn diagram package for enrichment analysis. The gene-pathway network was structured to obtain key target genes. In total, 124 active ingredients, 120 target genes of SFJDC and 251 NCP-related target genes were collected. The functional annotations cluster 1 of 23 candidate genes (CGs) were related to lung and Virus infection. RELA, MAPK1, MAPK14, CASP3, CASP8 and IL6 were the key target genes. The results suggested that SFJDC cloud be treated COVID-19 by multi-compounds and multi-pathways, and this study showed that the mechanism of traditional Chinese medicine (TCM) in the treatment of disease from the overall perspective.

Efficacy and safety of Shufeng Jiedu capsule for coronavirus disease 2019 (COVID-19): A protocol for systematic review and meta-analysis.

BACKGROUND: From the end of 2019 to the present, coronavirus disease 2019 (COVID-19) has put considerable pressure on the worlds medical system and caused significant mortality and economic losses around the world. In China, the Shufeng Jiedu capsule has been widely used in the treatment of COVID-19, but there is still a lack of evidence-based medical evaluation. METHODS: According to the retrieval strategies, randomized controlled trials (RCTs) on the Shufeng Jiedu capsule for COVID-19 were obtained from CNKI, WanFang, VIP, PubMed, Embase and Cochrane Library, regardless of publication date, or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the studies. The meta-analysis was performed using RevMan 5.3 and STATA 14.2 software. Ultimately, the evidentiary grade for the results will be evaluated. RESULTS: This study will evaluate the efficacy and safety of the Shufeng Jiedu capsule in the treatment of COVID-19 and provide a more reasonable choice of medication in clinical practice. CONCLUSION: Our findings will provide references for future clinical decision and guidance development. REGISTRATION: INPLASY registration number: INPLASY202070024.

[Analysis of 131 cases of COVID-19 treated with Ganlu Xiaodu Decoction].

In this study, Donghua Hospital information management system and Meikang clinical pharmacy management system were used to collect medical records of all inpatients diagnosed as coronavirus disease 2019(COVID-19) in Wuhan Third Hospital. The statistics was based on the data of the cases treated with Ganlu Xiaodu Decoction, including demographic statistics, clinical cha-racteristics before medication, outcome of after medication and efficacy of drug combination. Excel 2003 and SPSS Clementine 12.0 software were used to conduct statistics on the included cases, and Apriori algorithm and association rules were used for the association analysis on drug combination. A total of 131 cases of COVID-19 were treated with Ganlu Xiaodu Decoction combined with Chinese and Western medicine. All of the patients were cured and discharged. The drug combination mainly included Ganlu Xiaodu Decoction, abidor, Lianhua Qingwen, moxifloxacin, Qiangli Pipa Lu, vitamin C, glycyrrhizinate diammonium, pantoprazole and Shufeng Jiedu. There is a certain regularity and effectiveness in the treatment of COVID-19 infection patients with the combination of Ganlu Xiaodu Decoction and other drugs, but the rationality and safety still need to be further verified.

[Analysis on clinical study protocols of traditional Chinese medicine for coronavirus disease 2019].

To analyze the registered clinical trial protocols of traditional Chinese medicine(TCM) for the prevention and treatment of coronavirus disease 2019(COVID-19), in order to provide information for improving the quality of research design. The website of the Chinese Clinical Trial Registry(www.chictr.org.cn) and the American Clinical Trial Registry(clinicaltrials.gov) were searched to collect protocols of TCM for COVID-19. Documents were screened following the inclusion criteria, and data were extracted in regard to registration date, study objective, type of design, sponsor, patient, sample size, intervention, and evaluation index. Descriptive analysis was conducted. A total of 49 clinical trial protocols of TCM for COVID-19 were included. Primary sponsors were mainly hospitals or universities in places like Hubei, Beijing, Zhejiang and other regions. The implementation units are mainly in Hubei, Guangdong, Zhejiang, Henan and other regional hospitals. The types of study design were mainly experimental studies(40), including 30 randomized parallel controlled trials, 7 non-randomized controlled trials, 2 single arm trials and 1 consecutively recruited trial; besides, there were also 6 observational studies, 2 health service studies and 1 preventive study. The sample size reached a total of 30 562 cases, with a maximum of 20 000 for a single study and a minimum of 30. The 49 trials subjects included healthy people(3), isolation and observation cases(1), suspected cases(10),confirmed COVID-19 patients(31) and COVID-19 recovery patients(4). Of the 31 trials planned to include confirmed COVID-19 patients, 16 protocols no definite disease classification, 3 with a clear exclusion of severe subjects, 4 with common subjects, 2 with light, common or severe subjects, 1 with light and common subjects, 1 with common or severe subjects, 3 with severe subjects, and 1 with severe or critical subjects. The experimental interventions included Chinese patent medicine(Lianhua Qingwen Capsules/Granules, Huoxiang Zhengqi Dropping Pills/Oral Liquid, Babao Dan, Gubiao Jiedu Ling, Jinhao Jiere Granules, Compound Yu-xingcao Mixture, Jinye Baidu Granules, Shufeng Jiedu Capsuless, Shuanghuanglian Oral Liquid, Tanreqing Injection, Xuebijing Injection, Reduning Injection, Xiyanping Injection), Chinese medicinal decoction and taichi. The primary evaluation outcomes mainly included antipyretic time, clinical symptom relief, novel coronavirus nucleic acid turning to negative, conversion rate of severe cases and chest CT. There was a quick response of clinical research on the prevention and treatment of COVID-19 with TCM, with the current registered protocols covers the whole process of disease prevention, treatment and rehabilitation. However, issues need to be concerned, including unclear definition of patient's condition, unclear research objectives, unclear intervention process and inappropriate outcomes, etc. In addition, researchers should consider the actual difficulties and workload of doctors in epidemic response environment, and make effort to optimize the process and improve the operability of research protocols under the principle of medical ethics.

Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment.

Pneumonia associated with the 2019 novel coronavirus (2019-nCoV) is continuously and rapidly circulating at present. No effective antiviral treatment has been verified thus far. We report here the clinical characteristics and therapeutic procedure for four patients with mild or severe 2019-nCoV pneumonia admitted to Shanghai Public Health Clinical Center. All the patients were given antiviral treatment including lopinavir/ritonavir (Kaletra®), arbidol, and Shufeng Jiedu Capsule (SFJDC, a traditional Chinese medicine) and other necessary support care. After treatment, three patients gained significant improvement in pneumonia associated symptoms, two of whom were confirmed 2019-nCoV negative and discharged, and one of whom was virus negative at the first test. The remaining patient with severe pneumonia had shown signs of improvement by the cutoff date for data collection. Results obtained in the current study may provide clues for treatment of 2019-nCoV pneumonia. The efficacy of antiviral treatment including lopinavir/ritonavir, arbidol, and SFJDC warrants further verification in future study.