Amino Acid Sequence ; Coronavirus/drug effects* ; Coronavirus Infections/drug therapy* ; Drug Design ; Humans ; Protein Structure, Secondary ; Spike Glycoprotein, Coronavirus/metabolism* ; Viral Fusion Protein Inhibitors/pharmacology* ; Viral Fusion Proteins/metabolism*

Betacoronavirus ; COVID-19 ; China ; Coronavirus Infections/therapy* ; Humans ; Pandemics/prevention & control* ; Pneumonia, Viral/therapy* ; SARS-CoV-2

Corona virus disease 2019 (COVID-19) is a new type of coronavirus pneumonia, which is caused by infection of a novel coronavirus, SARS-CoV-2. The virus infects lung cells by binding angiotensin-converting enzyme 2 (ACE2) of cell surface, which leads to leukocyte infiltration, increased permeability of blood vessels and alveolar walls, and decreased surfactant in the lung, causing respiratory symptoms. The aggravation of local inflammation causes cytokine storm, resulting in systemic inflammatory response syndrome. In December 2019, a number of new pneumonia cases were reported by Wuhan Municipal Health Commission, after then a novel coronavirus was isolated and identified as SARS-CoV-2. To the date of Sep. 13th, 2020, COVID-19 is affecting 216 countries or regions, causing 28 637 952 cases, 917 417 deaths, and the mortality rate is 3.20%. This review will summarize the structure of SARS-CoV-2 and the pharmaceutical treatment of COVID-19, and their potential relationships.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/drug therapy* ; Humans ; Pandemics ; Pneumonia, Viral ; SARS Virus ; SARS-CoV-2

At present, SARS-CoV-2 is raging, and novel coronavirus pneumonia (COVID-19) has caused more than 35 million confirmed patients and more than 500 000 cases death, which seriously endanger human health, socioeconomic development, as well as global medical and public health systems. COVID-19 is highly contagious, has a long incubation period, and causes many death cases due to lack of effective specific treatment. Mesenchymal stem cells have powerful anti-inflammatory and immunoregulatory functions, and can effectively reduce the cytokine storm caused by coronavirus in patients, and improve the pulmonary fibrosis of patients, promote the repair of damaged lung tissue, and reduce the mortality. Currently, a number of related clinical trials of mesenchymal stem cell treatment of COVID-19 have been conducted, and have confirmed the safety and efficacy, suggesting a good clinical application prospect. While progress has been made in mesenchymal stem cell therapy for COVID-19, we should also catch sight of the problems and challenges faced by mesenchymal stem cell clinical trials under severe epidemic situation, including clinical trials design, stem cell quality management, and ethics in treatment. Only by paying attention to these can we guarantee the safe and effective development of mesenchymal stem cell clinical trials in the treatment of COVID-19.
Betacoronavirus ; COVID-19 ; Clinical Trials as Topic ; Coronavirus Infections/therapy* ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology* ; Pandemics ; Pneumonia, Viral/therapy* ; SARS-CoV-2

Coronavirus disease 2019 (COVID-19) has spread widely on a large scale in the whole world at present, seriously endangering human health. There are still no effective and specific drugs, so it is urgent to find safe and effective therapeutic methods. Mesenchymal stem cells (MSCs) have many biological functions of powerful immunomodulation and tissue repair and regeneration. As a stem cell therapy, it has the potential to reduce the tissue injury and mortality in severe patients infected with novel coronavirus. At present, many research institutions in China and abroad have started a number of clinical research projects about MSCs in the treatment of COVID-19. In addition, those projects have initially confirmed the safety and effectiveness of this therapy. Therefore, this research field has been proved to have a very good clinical therapy prospect.
Betacoronavirus ; COVID-19 ; China ; Coronavirus Infections/therapy* ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology* ; Pandemics ; Pneumonia, Viral/therapy* ; SARS-CoV-2

On May 15, 2020, the Lancet published an article titled Use of Herbal Drugs to Treat COVID-19 Should be with Caution. While this is true of all drugs, herbal and otherwise, the data may be biased and deserve a scientific response. We believe these types of reports will unfairly and negatively impact the field of integrative medicine as a whole, and must be answered with facts and statistics that more accurately represent the current situation.
Betacoronavirus ; Bias ; COVID-19 ; Coronavirus ; Coronavirus Infections/drug therapy* ; Drugs, Chinese Herbal ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2

With the global outbreak of coronavirus disease 2019(COVID-19), screening of effective drugs has became the emphasis of research today; furthermore, screening of Chinese classic prescriptions has became one of the directions for drug development. This study analyzed the application of classic prescriptions in the diagnosis and treatment schemes based on the Diagnosis and Treatment Schemes for Coronavirus Disease at the country, provincial and municipal levels, and further explored its disrobing effect on COVID-19 disease severe phase network, and selected representative prescriptions for core target screening and gene enrichment analysis, so as to reveal its mechanism of action. Among them, 13 prescriptions were found to be used for 10 times or more, including Maxing Shigan Tang, Yinqiao San, Shengjiang San, Dayuan Drink, Xuanbai Chengqi Decoction. In addition, the COVID-19 efficacy prediction analysis platform(TCMATCOV platform) was used to calculate the network disturbances of the Chinese classic prescriptions involved. Based on the prediction results, 68 classic prescriptions were assessed on the COVID-19 disease network robustness disturbance. The average disturbance scores for the interaction confidence scores were ranked to be 0.4, 0.5, and 0.6 from the highest to the lowest. There were 7 prescriptions with a score of 17 or more, and 50 prescriptions with a score of 13 or more. Among them, the top three prescriptions were Ganlu Xiaodu Dan(18.19), Lengxiao Wan(17.74), and Maxing Shigan Tang(17.62). After further mining the action targets of these three prescriptions, it was found that COVID-19 disease-specific factors Ccl2, IL10, IL6 and TNF were all the targets of three prescriptions. Through the enrichment analysis of the biological processes of the core targets, it was found that the three prescriptions may prevent the development of the disease by affecting cell-to-cell adhesion, cytokine-mediated signaling pathway, and chronic inflammatory responses to COVID-19 at the severe phase. This study showed that the TCMATCOV platform could evaluate the disturbance effect of different prescriptions on the COVID-19 disease network, and predict potential effectiveness based on the robustness of drug-interfered pneumonia disease networks, so as to provide a reference for further experiments or clinical verification.
Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral ; drug therapy

According to the classification of traditional Chinese medicine syndromes of coronavirus disease 2019 by the national competent authority, this study determined that human coronavirus 229 E(HCoV-229 E) was infected in a mouse model of cold and dampness syndrome, so as to build the human coronavirus pneumonia with pestilence attacking lung syndrome model. The model can simulate the traditional Chinese medicine treatment of common disease syndromes in Coronavirus Disease 2019 Diagnosis and Treatment Program(the sixth edition for trial). Specific steps were as follows. ABALB/c mouse model of cold and dampness syndrome was established, based on which, HCoV-229 E virus was infected; then the experiment was divided into normal control group, infection control group, cold-dampness control group, cold-dampness infection group(the model group), high-dose Chaiyin Particles group(8.8 g·kg~(-1)·d~(-1)), and low-dose Chaiyin Particles group(4.4 g·kg~(-1)·d~(-1)). On the day of infection, Chaiyin Particles was given for three consecutive days. Lung tissues were collected the day after the last dose, and the lung index and inhibition rate were calculated. The nucleic acid of lung tissue was extracted, and the HCoV-229 E virus load was detected by Real-time fluorescent quantitative RT-PCR. Blood leukocytes were separated, and the percentage of T and B lymphocytes was detected by flow cytometry. Lung tissue protein was extracted, and IL-6, IL-10, TNF-α and IFN-γ contents were detected by ELISA. High and low-dose Chaiyin Particles significantly reduced the lung index(P<0.01) of mice of human coronavirus pneumonia with pestilence attacking the lung syndrome, and the inhibition rates were 61.02% and 55.45%, respectively. Compared with the model control group, high and low-dose Chaiyin Particles significantly increased cross blood CD4~+ T lymphocytes, CD8~+T lymphocytes and total B lymphocyte percentage(P<0.05, P<0.01), and reduced IL-10, TNF-α and IFN-γ levels in lungs(P<0.01). In vitro results showed that TC_(50), TC_0, IC_(50) and TI of Chaiyin Particles were 4.46 mg·mL~(-1), 3.13 mg·mL~(-1), 1.12 mg·mL~(-1) and 4. The control group of in vitro culture cells had no HCoV-229 E virus nucleic acid expression. The expression of HCoV-229 E virus nucleic acid in the virus control group was 1.48×10~7 copies/mL, and Chaiyin Particles significantly reduced HCoV-229 E expression at doses of 3.13 and 1.56 mg·mL~(-1), and the expression of HCoV-229 E nucleic acid was 9.47×10~5 and 9.47×10~6 copies/mL, respectively. Chaiyin Particles has a better effect on the mouse model with human coronavirus pneumonia with pestilence attacking the lung syndrome, and could play a role by enhancing immunity, and reducing inflammatory factor expression.
Animals ; Coronavirus 229E, Human ; Coronavirus Infections ; immunology ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Lung ; immunology ; virology ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred BALB C

The epidemic situation of coronavirus disease 2019(COVID-19) is developing rapidly in the world, and the influence is serious. In this study, the prescription of Mongolian medicine to prevent new type of COVID-19 was investigated. Based on the second edition and the third edition of COVID-19 Mongolian Medicine Prevention and Treatment Guidance Program issued by the Inner Mongolia Autonomous Region Health Commission, using Excel 2007, SPSS Modeler 18, SPSS Statistics 25, Cytoscape 3.7.1 statistical software as a tool, the association rules analysis and cluster analysis of Mongolian medicine included in the standard were carried out. Among the 45 prophylactic prescriptions included in the standard, a total of 34 high-frequency drugs using frequency ≥5 were used, of which Carthami Flos(21 times, 4.46%), Chebulae Fructus(20 times, 4.26%), Moschus(13 times, 2.77%), Myristicae Semen(12 times, 2.55%), Santali Albi Lignum(12 times, 2.55%), and Bovis Calculus(12 times, 2.55%) were the most common. The main drugs for the prevention of COVID-19 were Liang(13 times, 38.23%), Wen(9 times, 26.47%), the flavor was Ku(20 times, 34.48%), Xin(13 times, 22.41%), Gan(11 times, 18.97%), the most used drugs treating hot evil(99 times, 32.46%), treatment of "Heyi" drugs(51 times, 16.72%), treatment of "Badagan" drugs(40 times, 13.11%), treatment of "sticky" drugs(37 times, 12.13%), and a cough, eliminating phlegm and antiasthmatic(31 times, 10.16%), the association rule analysis found that the highest association intensity of the drug pair combination of 11. Clustering analysis using the cluster analysis of inter-group join method found a total of 8 categories. In this study, 45 prescriptions of Mongolian medicine for the prevention of COVID-19 were collec-ted and further analyzed, hoping to provide new ideas for clinical diagnosis and treatment.
Betacoronavirus ; China ; Coronavirus Infections ; drug therapy ; Humans ; Medicine, Mongolian Traditional ; Pandemics ; Pneumonia, Viral ; drug therapy

The coronavirus disease 2019(COVID-19) is developing rapidly and posing great threat to public health. There is no effective intervention for the severe patients, and their prognosis is poor. It is worth noting that in the fight against COVID-19, China has always put equal emphasis on both Chinese and Western medicine. Traditional Chinese medicine has played an important role in the whole process. It is of great significance to discuss the rules and characteristics of the prescription of traditional Chinese medicine in the treatment of COVID-19. In this study, information was collected from 444 severe COVID-19 patients who were admitted to a hospital designated to treat patients with severe COVID-19 in Wuhan before March 20, 2020. We collected traditional Chinese medicine prescriptions for patients with severe COVID-19, referred to Chinese Pharmacopoeia to standardize the names of traditional Chinese medicine, and extract the property, flavor and channel tropism of traditional Chinese medicines to analyze the rules of the prescriptions. IBM SPSS Modeler 18.0 software was used to conduct correlation analysis of traditional Chinese medicine. Effective traditional Chinese medicines against COVID-19 was identified by the TCMATCOV platform. In the end, 1 532 effective prescriptions were included. Among them, the high-frequency drugs are Poria, Astragali Radix, Pogostemonis Herba, Armeniacae Semen Amarum, Atractylodis Macrocephalae Rhizoma, Pinelliae Rhizoma, Glycyrrhizae Radix et Rhizoma, Magnoliae Officinalis Cortex, Ephedrae Herba, Cinna-momi Ramulus. Most of the drugs have the following functions: resolving dampness, replenishing deficiency, resolving phlegm, cough, and asthma. The core combinations are Pogostemonis Herba-Poria, Astragali Radix-Pogostemonis Herba-Poria, Amomi Fructus-Poria, Amomi Fructus-Pogostemonis Herba, Amomi Fructus-Astragali Radix. The majority of the medicines are with cold and warm properties, and the proportions are 41.03% and 38.46%, respectively. The medicinal flavors are mainly concentrated in sweet and bitter, and the proportions are 34.71% and 30.58%, respectively. The meridian of the drug is more into the lung, stomach and spleen, with lung accounting for 22.87%. From the analysis of high-frequency drugs to the core combinations, one can see that the main treatment principle for severe COVID-19 is to remove internal and external dampness, protect the spleen and stomach, remove evil energy, and support righteousness. TCMATCOV platform was used to calculate the network disturbances of the high-frequency drugs. It was found that the traditional Chinese medicine with a high disturbance score accounted for a high proportion of the classic anti-COVID-19 prescriptions used by clinicians. Among them, the drugs with top scores are Ephedrae Herba, Citri Reticulatae Pericarpium, Eupatorii Herba, Platycodonis Radix, Cinnamomi Ramulus, Astragali Radix, Magnoliae Officinalis Cortex, Atractylodis Macrocephalae Rhizoma, Pogostemonis Herba, Scutellariae Radix. After a further exploration of the action targets, it was showed that disease-specific factor TNF was the target of the above ten drugs, and traditional Chinese medicine can exert anti-inflammatory and immune-modulating effects.
Betacoronavirus ; China ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral ; drug therapy