The coronavirus disease 2019(COVID-19) is raging in China and more than 20 other countries and regions since the middle of December 2019. Currently, there is no specific drug or vaccine besides symptomatic supportive therapy. Taking full advantage of the clinical experience of traditional Chinese medicine(TCM) in preventing and controlling major epidemics such as SARS, it is an important mission for TCM to propose effective formula with immediate response and solid evidence by using modern biomedical knowledge and techniques(molecular docking assisted TCM formulation for short). In view of the high homology between the gene sequences of the novel coronavirus and SARS virus, and the similarities between the two in terms of pathogenic mechanism and clinical manifestations, our team established a rapid screening and optimization model for the prevention and treatment of the novel coronavirus based on clinical experience and molecular docking technology. Firstly, the clinical team and the research team pre-developed and screened TCM formula by using "back-to-back" manner. Then, the formula was optimized and determined by comparing and analyzing the results of the two groups. The results showed that the research team screened out 46 active ingredients from candidate TCMs that could act on the novel coronavirus S-protein-binding site of human ACE2 protein, which were mainly attributed to 7 herbs such as Lonicerae Japonicae Flos and Mori Folium. The result was largely consistent with the formula raised by the clinical group, verifying and supporting its rationality. This provides evidence for the scientific and potential efficacy of the TCM prescription from the perspective of treatment target analysis, and also suggests that the TCM prescription has the potential to directly inhibit viral infection in addition to improving clinical symptoms or syndromes. Based on this, our team optimized and formed a new anti-coronavirus TCM prescription "Keguan Yihao", immediately providing the TCM prescription with certain clinical experience and objective evidence support for the prevention and treatment of new emergent infectious diseases in our hospital. The TCM prescription was combined with modern medicine symptomatic supportive treatment for clinical treatment, preliminary results showed better effect than symptomatic supportive therapy alone. This research has innovated the method mode in clinical practice and basic research integration of traditional Chinese medicine for the prevention and control of new emerging infectious diseases. It is of great significance to further improve the rapid response mechanism of TCM in face of major epidemics, and further improve the capability level of TCM to prevent and treat new emerging infectious diseases.
Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/pharmacology* ; Betacoronavirus ; COVID-19 ; China ; Coronavirus Infections/drug therapy* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Pandemics ; Peptidyl-Dipeptidase A/chemistry* ; Pneumonia, Viral/drug therapy* ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/chemistry* ; COVID-19 Drug Treatment

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
Administration, Inhalation ; Adult ; China ; Coronavirus Infections ; diagnosis ; drug therapy ; mortality ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Integrative Medicine ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; mortality ; Risk Assessment ; Severe Acute Respiratory Syndrome ; diagnosis ; drug therapy ; mortality ; Severity of Illness Index ; Survival Rate

Objective:To discuss the effect of modified Yangxintang on chronic pulmonary heart disease (CPHD) with syndrome of deficiency of heart and lung Qi and progress of disease. Method:One hundred and twenty-eight patients were randomly divided into control group 64 cases and observation group 64 cases by random number table. Patients in control group got comprehensive rehabilitation measures of western medicine. Those who had respiratory distress got Salmeterol ticasone powder inhaler, 1-2 times/day, 1 inhale/time.And those who had cough and phlegm got Ambroxol hydrochloride tablets for 1-2 week, 1-2 tablet/time, 3 times/day. In addition to the therapy of control group, patients in observation group was also added with modified Yangxintang, 1 dose/day, 5 days/week. Record the and times of acute aggravate and cold, pulmonary artery systolic pressure (PASP), mean pulmonary artery pressure (MPAP), left ventricular ejection fraction (LVEF), stroke volume (SV) and cardiac output (CO) were recorded during 48 weeks. Before and after treatment, scores of modified British medical research council respiratory questionnaire (mMRC questionnaire), Minnesota Heart Failure Quality of life scale (MLHFQ), syndrome of deficiency of heart and lung Qi and 6-minute walking test (6 MWT) were scored. And levels of N-terminal B-type natriuretic peptide (NT-proBNP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), endothelin (ET-1), CD3⁺, CD4⁺, CD8⁺ and CD4⁺/CD8⁺ were detected. Result:The clinical efficacy in observation group was better than that in control group (Z=2.108, P<0.05). During 48 weeks of observation period, times of acute aggravate and cold in observation group were less than those in control group (P<0.01). Levels of PASP, MPAP and NT-proBNP were lower than those in control group (P<0.01). And levels of LVEF, SV, CO, 6 MWT and NO were higher than those in control group (P<0.01), levels of CD3⁺, CD4⁺ and CD4⁺/CD8⁺ were higher than those in control group (P<0.05). And levels of mMRC, MLHFQ, score of syndrome of deficiency of heart and lung Qi, TNF-α , IL-6, ET-1, CD8⁺ and were all lower than those in control group (P<0.01, P<0.05). Conclusion:In addition to anti-inflammatory, anti-asthmatic and anti-tussive therapies, modified Yangxintang can improve the immune function, relieve the symptoms of heart and lung, improve the function of heart and lung and the quality of life, inhibit the inflammatory reaction, improve the function of vascular endothelium, reduce the pulmonary hypertension, control the progress of disease.