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*

Chloroquines are the long-established prescription drug, which are often used clinically to treat malaria and connective tissue diseases. Since December 2019, corona virus disease 2019 （COVID-19） outbreaks caused by 2019 novel coronavirus （2019-nCoV） has occurred in China and many countries around the world. Due to the lack of drugs against COVID-19, the disease spreads rapidly and the mortality rate is relatively high. Therefore, specific drugs against 2019-nCoV need to be quickly screened. The antimalarial drug chloroquine phosphate which has already been approved is confirmed to have an anti-2019-nCoV effect and has been included in diagnostic and therapeutic guidelines. However, awareness of the risk of chloroquine phosphate causing acute poisoning or even death should be strengthened. The current dosage recommended in clinical treatment is larger than that in previous treatment of malaria and the period of treatment is longer. Many provinces have required close clinical monitoring of adverse reactions. This paper reviews the pharmacological effects, poisoning and toxicological mechanisms, in vivo metabolism and distribution, and forensic issues of chloroquine drugs, in order to provide help to forensic practice and clinical work.
Betacoronavirus ; COVID-19 ; China ; Chloroquine/therapeutic use* ; Coronavirus Infections/drug therapy* ; Forensic Toxicology ; Humans ; Pandemics ; Pneumonia, Viral/drug therapy* ; SARS-CoV-2 ; COVID-19 Drug Treatment

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

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

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

With the rapid outbreak of COVID-19, traditional Chinese medicine(TCM) has been playing an active role against the epidemic. However, the screening of TCM is limited by the development cycle and laboratory conditions, which greatly limits the screening speed. This study established optimization docking models and virtual screening to discovery potential active herbs for the prevention and treatment of the novel coronavirus based on molecular docking technology. The crystal structures of 3 CL protease(Mpro) and papain-like protease(PLP) were obtained from PDB database and homologous modeling respectively, and were used to conduct virtual screening of TCMD 2009 database by CDOCKER program. The ingredients scored in the top 100 were selected respectively, and the candidate herbs were ranked by the numbers of hit molecules. Based on Mpro inhibitors screening, 12 322 potential active components were obtained, and the representative active components included aster pentapeptide A, ligustrazine, salvianolic acid B, etc., and Zingiberis Rhizoma Recens, Asteris Radix et Rhizoma, Notoginseng Radix et Rhizoma, Chuanxiong Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Zingiberis Rhizoma, Dianthi Herba, Rhei Radix et Rhizoma, Cistanches Herba were obtained. While 11 294 potential active ingredients were obtained by PLP inhibitor screening, representative active ingredients included gingerketophenol, ginkgol alcohol, ferulic acid, etc., and Codonopsis Radix, Notopterygii Rhizoma et Radix, Zingiberis Rhizoma Recens, Ginkgo Semen, Chuanxiong Rhizoma, Trichosanthis Fructus, Paeoniae Radix Alba, Psoraleae Fructus, Sophorae Flavescentis Radix, Notoginseng Radix et Rhizoma, Angelicae Sinensis Radix were chosen. By combining the diagnosis and treatment scheme of Hunan province's and angiotensin converting enzyme 2(ACE2) inhibitors screening from literature, present study also discussed the rational application of candidate herbs to this epidemic situation. Trichosanthis Fructus obtained by PLP inhibitors screening and Fritillaria verticillata obtained by ACE2 inhibitors screening were parts of the Sangbei Zhisou Powder and Xiaoxianxiong Decoction, which might be applicable to the syndromes of cough and dyspnea. Rhei Radix et Rhizoma screened by Mpro and Trichosanthis Fructus screened by PLP were contained in Maxing Shigan Decoction and Xuanbai Chengqi Decoction, and could be applied to the syndromes of epidemic virus blocking lung. Mori Folium, Lonicerae Japonicae Flos and Forsythiae Fructus obtained by ACE2 inhibitors screening were included in the Sangju Decoction and Yinqiaosan, which might be applicable to the syndromes of warm pathogen attacking lung and cough and dyspnea. The results of this study are intended to provide a reference for the further development of traditional Chinese medicine to deal with the new epidemic.
Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/pharmacology* ; Betacoronavirus/drug effects* ; COVID-19 ; Coronavirus Infections/drug therapy* ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Pandemics ; Peptidyl-Dipeptidase A ; Pneumonia, Viral/drug therapy* ; SARS-CoV-2 ; COVID-19 Drug Treatment

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.
Betacoronavirus ; COVID-19 ; China ; Clinical Trial Protocols as Topic ; Coronavirus Infections/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral/drug therapy* ; Randomized Controlled Trials as Topic ; Research Design ; SARS-CoV-2 ; COVID-19 Drug Treatment

The coronavirus disease 2019(COVID-19) is developing rapidly and posing great threat to public health. There is no specific medicine available for treating the disease. Luckily, traditional Chinese medicine has played a positive role in the fighting against COVID-19. In this paper, We collected and sorted the prescriptions of modern Chinese medicine for COVID-19 released by national government, different provinces, autonomous regions and municipalities, as well as online databases, such as CNKI, WanFang medical network, and VIP database. These prescriptions were combined with the inheritance of traditional Chinese medicine auxiliary V2.5, and the complex system entropy clustering method was used to determine the association rules and frequency of single drug and drug combination in the prescription. In the end, 96 effective prescriptions were included. Among them, the four properties were mainly concentrated in temperature, cold and level, the five tastes were mainly concentrated in bitter, hot and sweet, and the meridians were mainly concentrated in lung, stomach and spleen. The high-frequency drugs were Glycyrrhizae Radix et Rhizoma, Armeniacae Semen Amarum, Gypsum Fibrosum, etc., and the high-frequency combinations are Gypsum Fibrosum-Armeniacae Semen Amarum, Gypsum Fibrosum-Glycyrrhizae Radix et Rhizoma, Armeniacae Semen Amarum-Glycyrrhizae Radix et Rhizoma, the core combinations are Lepidii Semen-Armeniacae Semen Amarum-Gypsum Fibrosum, Pogostemonis Herba-Zingiberis Rhizoma Recens-Magnoliae Officinalis Cortex, Ophiopogonis Radix-Armeniacae Semen Amarum-Scutellariae Radix and so on. Form new prescriptions Lepidii Semen, Armeniacae Semen Amarum, Gypsum Fibrosum, Pogostemonis Herba, Zingiberis Rhizoma Recens, Magnoliae Officinalis Cortex. Ophiopogonis Radix, Armeniacae Semen Amarum, Scutellariae Radix, Schisandrae Sphenantherae Fructus, Panacis Quinquefolii Radix. From the medicinal properties to high-frequency drugs and new prescriptions, it could be seen that the overall treatment of COVID-19 by traditional Chinese medicine was to strengthen body resistance, eliminate pathogenic factors, and give attention to Qi and Yin.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/drug therapy* ; Data Mining ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral/drug therapy* ; SARS-CoV-2 ; COVID-19 Drug Treatment

Coronavirus disease 2019(COVID-19) triggered a severe and complicated epidemic situation, and it is of great significance to discuss the rules and characteristics of the prescription of COVID-19 in traditional Chinese medicine. This study collected prevention and treatment approaches of traditional Chinese medicine for COVID-19 released from the National Health Committee of China, 7 provinces and municipal health committees, the Chinese Medicine Administration and Handbook of Traditional Chinese Medicine Diagnosis and Treatment of COVID-19 between January 1 and February 18, 2020, and prescriptions prepared by 3 masters of Chinese medicine and 4 well-known Chinese medicine experts. These information were selected according to the inclusion and exclusion criteria, and EpiData 3.0 software was used to establish the "Traditional Chinese Medicine Prescription Library for the Prevention and Treatment of COVID-19" and the "Common Database of Traditional Chinese Medicine for the Prevention and Treatment of COVID-19". A total of 93 effective Chinese medicine prescriptions and a total of 157 kinds of constituent medicines were collected. Data analysis was performed by SPSS 18.0 software. The results showed that: ①most of the medicines are with cold and warm properties, 69 with cold medicines, accounting for 43.95%, 57 with warm medicines, accounting for 36.31%, and less with hot medicines, taking up 1.27%; ②there are many pungent, bitter and sweet medicines, and the distribution of medicinal flavors is different at different disease stage. The pungent medicines are mostly found in the early stage, the bitter drugs are the main flavor in the middle and severe stage, and the sweet medicines are mostly used in the recovery stage; ③the meridian of the drug is more concentrated at the lung, stomach, and heart, and most of drugs are into the lung meridian, accounting for 24.55%; these medicines are mostly into the lungs and stomach in the initial and middle stages, and into the heart and kidney in severe stages; ④oral drugs are mostly non-toxic, among which only 6 kinds are toxic, namely Armeniacae Semen Amarum, Dryopteridis Crassirhizomatis Rhizoma, Paridis Rhizoma, Pinelliae Rhizoma, Aconiti Lateralis Radix Praeparaia; ⑤most of the drugs have five types of functions: treating exterior syndromes, resolving dampness, clearing heat, replenishing deficiency, resolving phlegm, cough, and asthma. In the early stage, both drugs for treating exterior syndromes and heat clearing drugs were equally used, accounting for 18.81% each. In the middle stage, drugs resolving phlegm, cough, and asthma drugs are more often used, accounting for 29.61%. In the severe stage, heat clearing drugs are mostly used, accounting for 33.33%. During the recovery period, tonic deficiency drugs are used the most, accounting for 36.47%. The medical characteristics and efficacy of Chinese medicine in preventing and treating COVID-19 are closely related to the understanding of the etiology of Chinese medicine and the location and pathogenesis of the disease. Staged medication and local conditions need attention during the identification and treatment of COVID-19 clinical syndromes.
Betacoronavirus ; COVID-19 ; China ; Coronavirus Infections/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral/drug therapy* ; SARS-CoV-2 ; COVID-19 Drug Treatment

The outbreak of coronavirus disease 2019(COVID-19) seriously endangers people's health. Traditional Chinese medicine(TCM) has been recommended for the treatment of COVID-19 in Novel Coronavirus Pneumonia Prevention and Control Strategy, which have made outstanding contributions to the prevention and control of the epidemic. The wide application of Chinese medicine asked the pharmacists and doctors, nurses, and medical technicians in Wuhan and around the country to stand on the front line of COVID-19 treatment, and provide pharmaceutical care services, which has effectively guaranteed the safety and rational use of Chinese medicine. This article will introduce the TCM cognition of the COVID-19, analyze the clinical application of Chinese medicine and the entry point of pharmaceutical care, and clarify that clinical Chinese pharmacists can participate in making medication therapy plan, medication reconciliation, and prescription review, promoting rational drug use, pharmaceutical monitoring, and drug risk management. The participation of clinical Chinese pharmacists in the prevention and treatment of COVID-19 is conducive to improving the level of rational use of TCM, by ensuring the effectiveness, and safety.
Betacoronavirus ; COVID-19 ; China ; Coronavirus Infections/drug therapy* ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pharmaceutical Services/organization & administration* ; Pneumonia, Viral/drug therapy* ; SARS-CoV-2 ; COVID-19 Drug Treatment