The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout China and many other countries around the world. The antivirals are important measures to this epidemic; however, there is no drug approved for against coronavirus yet. With the continuously rising number of confirmed/suspected cases of COVID-19, it is urgent to obtain antiviral drugs for the clinical treatment. In response to this situation, drug repurposing strategy becomes one of the best approaches for anti-SARS-CoV-2 drug discovery. By retrieving the clinical trials registered in Chinese Clinical Trial Registry and ClinicalTrials.gov, a total of 14 chemical drugs were registered for COVID-19. In this review, we summarize and analyze the 14 drugs' indications, targets, and research basis related to the activities against viral infections, esp. coronavirus infections. We are making efforts to understand the evidence basis of these drugs for the treatment of SARS-CoV-2 infection applied by various research and clinical institutions in response to this COVID-19 outbreak, and also providing clues for quick response to possible epidemic in future and reasonable expansion of the indications of drugs.

"TCM syndrome of plague attack lung" is a classification of traditional Chinese medicine syndromes of the novel coronavirus pneumonia by the Beijing Municipal Administration of Traditional Chinese Medicine. In this study, a mouse model combining disease with syndrome of human coronavirus pneumonia with cold-dampness pestilence attacking the lung was established for the first time, and the therapeutic effect of matrine sodium chloride injection was evaluated based on immune regulation and inflammatory damage. Lung index, lung index inhibition rate and HE stain were used to evaluate the therapeutic effect of matrine sodium chloride injection on the model mice; the viral load in lung tissue was measured by RT-PCR to evaluate its antiviral effect; the percentage of CD4⁺T cells, CD8⁺T cells and B cells were detected by flow cytometry to evaluate its immunomodulatory effect; the production of interleukin 6 (IL-6), IL-10, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by ELISA to evaluate its anti-inflammatory effect. All interventions and operations in the experiment were approved by the Animal Ethics Committee of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, and conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH) and Beijing Experimental Animal Ethics Committee. The results showed that intraperitoneal injection of the high-dose (36.67 mL·kg^-1·d^-1) and low-dose (18.33 mL·kg^-1·d^-1) of matrine sodium chloride injection significantly improved the pathological damage of lung tissue and reduced lung index. The lung index inhibition rates were 86.86% and 76.53%, respectively. The production of IL-6, IL-10, TNF-α, IFN-γ, as well as the viral load in lung tissue were reduced significantly compared to the model; the percentage of CD4⁺T cells, CD8⁺T cells and B cells in peripheral blood were increased compared to the model. These results indicated that the matrine sodium chloride injection has an evident therapeutic effect on the model, and its mechanism was related to the inhibition virus replication, regulation of immunity function and inhibition of inflammatory factor release. This study provided laboratory data support for matrine sodium chloride injection which was used to treat the novel coronavirus pneumonia in clinical in Hubei province. These results indicated that the matrine sodium chloride injection has a good prospect for prevention and treatment of the novel coronavirus pneumonia.

HPLC-RID and HPIC-CD methods were established for the determination of sucrose octasulfate content in irinotecan hydrochloride liposomes for injection. HPLC-RID:This method was performed on a Kromasil 100-5-NH₂ column (250 mm×4.6 mm, 5 μm) with a mobile phase of 0.8 mol·L^-1 ammonium sulfate buffer (pH 3.5)-acetonitrile (83:17). The flow rate, column temperature and detector temperature were maintained at 1 mL·min^-1, 30℃ and 30℃ respectively. HPIC-CD:This method was performed on an anion exchange column Dionex InPac^TM AS11-HC (250 mm×4 mm, 9 μm) with an eluent of 30 mmol·L^-1 sodium hydroxide solution. The flow rate was 1.5 mL·min^-1, the column temperature was 30℃ and the detector temperature was 35℃. The HPLC-RID method and HPIC-CD method were validated with respects to specificity, limit of detection, limit of quantitation, linearity, precision, accuracy, stability and robustness and met the validation requirements. There were no significant differences between the HPIC-CD and HPLC-RID methods according to T-test analysis, both of which were applicable for the measurement of sucrose octasulfate concentration in irinotecan hydrochloride liposomes for injection. However, the HPLC-CD was better at the following aspects:higher detection sensitivity, simpler sample pretreatment, lower time and money spent, better environmental protection.

Nitric oxide (NO) is widely present in peripheral and central nervous system and regulates many physiological functions. Sleep-arousal is an advanced physiological activity. Studies have shown that NO is involved in the regulation of sleep and arousal. Nitric oxide synthases (NOSs) are a family of enzymes that catalyze the production of NO from L-arginine. Through guanylate cyclase or S-nitrosation of protein, NO can affect the activity of the ascending reticular activating system to regulate the sleep-arousal process. This paper summarizes the production of NO, its effect on sleep-arousal and its mechanism in the ascending reticular activating system, and provides new ideas and directions for the study of sleep and arousal.

Higenamine (HG) is an active cardiotonic component isolated from Aconite. Chinese and foreign scholars have done a lot of research on the metabolism and pharmacological effects of HG, which confirmed that it has cardiovascular pharmacological effects of cardiactonic action and vasodilation for the treatment of heart failure and bradycardia, anti-oxidative and anti-apoptotic effects which can be used to protect the heart and reduce heart ischemia and reperfusion injury. In addition, HG inhibits the expression of iNOS mRNA by inhibiting the activity of the transcription factor NF-κB, inhibits the lipopolysaccharide (LPS)-induced NO product, and inhibits platelet aggregation and thrombus formation, thereby improving the experimental septic shock in animals. This article reviews the recent progress in cardiovasular pharmacology of HG, which will contribute to the further development and clinical application of it in the future.

"Kidney essence" is a profound concept in the theory of traditional Chinese medicine. But its biological basis is unknown until now, resulting in the therapeutic effects of traditional Chinese drugs on reinforcing kidney for supplementing essence hard to be evaluated. This study aimed, to explore the potential biological basis and mechanism of traditional Chinese drugs of reinforcing kidney for supplementing essence on diseases related to deficiency of kidney essence through network pharmacology analysis on the intersection of targets of drugs and diseases. The targets for ingredients in Rehmanniae radix praeparata (RRP), Polygoni multiflori radix praeparata (PMRP) and Polygonati rhizome (PR) were gathered from TCMSP and TCMID database. Osteoporosis, Alzheimer's disease, anemia, infertility and oligospermia targets were collected from OMIM and DisGeNET database. Drug-compound-target-disease (DCTD) network was established with Cytoscape 3.6.1 software, then Clue GO and DAVID database was used to acquire the annotation about GO terms and signaling pathways. Natural aging mice, an acknowledged syndrome model of deficiency of kidney essence, and RRP were used to verify the predictive targets by Western blot analysis. All animal experiments were conducted in accordance with the international guidelines and regulations for the care and use of animals. DCTD network showed that the intersection of drugs and diseases included 175 common targets. After topology analysis, 71 key were screened out targets which were associated with GO annotation exhibited that biological processes (including transcription regulation, RNA metabolism regulation, and DNA-dependent transcription regulation), cell composition (including nuclear lumen, organelle lumen, and membrane closure lumen), molecular function (including transcription regulation, transcription factor activity, and enzyme binding), and signaling pathway (including peroxisome proliferator-activated receptor alpha (PPARα), mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1 (HIF-1), erythropoietin (EPO) and other signaling pathways. In natural aging mice, the expressions of HIF-1α, growth factor receptor-bound protein 2 (GRB2), MAPK3, signal transducer and activator of transcription 5A (STAT5A), transcription factor AP-1 (JUN) and proto-oncogene c-Fos (FOS) in EPO pathway were significantly decreased. RRP significantly reversed the decrease of the above targets. Above all, these results indicated that the therapeutic effects of traditional Chinese drugs of reinforcing kidney for supplementing essence on deficiency of kidney essence may be related to the regulation of nuclear transcriptional activity and EPO signaling pathway.

Atherosclerosis is one of the causes of many cardiovascular diseases. Lipid metabolism disorder is an important risk factor for atherosclerosis. Lipase-targeted screening may help discovery of hypolipidemic and anti-atherosclerotic drugs. Traditional methods for enzyme-based screening exhibit drawbacks of tedious operation steps, reduced enzyme activity, slow mass transfer, as well as high false positive rate. In this paper, an integrated perfusion enzyme affinity selection system based on hollow fiber was constructed to screen hypolipidemic and anti-atherosclerotic compounds from traditional Chinese medicines, and the total saponins of Kudingcha were taken as a case. First, we built a hollow fiber based perfusion system and optimized the methodology for enzyme affinity selection. Then, two active compounds of kudinosides A and C were identified as potential lipase inhibitors from the total saponins of Kudingcha by the proposed system. Last, the activity of kudinosides A and C was verified by lipase inhibitory assay and formation of foam cell model induced by low density lipoprotein aggregates, exhibiting the reliability of the system. This platform shows the advantages of integration, fast mass transfer, simple operation, low cost, as well as improved throughput and efficiency, which is especially suitable for rapid screening active components from traditional Chinese medicine.

In this study, an immunostimulating particulate β-glucan was isolated from a hot alkaline extract of the fruiting bodies of Ganoderma lucidum. The optimum conditions of 8 hours treatment time, 1:20 solid-liquid ratio and 55℃ for the alkaline extract process were obtained after investigating by single-factor experiments and Box-Benhnken design in terms of the Ganoderma lucidum particulate β-glucan (GLG) increment, and these conditions resulted in a GLG yield of 8.57%. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. The result showed that resident macrophages were effectively activated by GLG, such as with the up-regulation of co-stimulatory molecules, the secretion of cytokines and phagocytic uptake. GLG could also promote the proliferation of spleen lymphocytes in mice. In addition, IFN-γ production of spleen CD4⁺T cells and cytotoxic T lymphocyte (CTL) responses were significantly enhanced on GLG orally treatment, which ultimately resulted in significantly decreased tumor burden. Taken together, these data suggest that GLG might act as an immune stimulator to exert antitumor effects.

Recently, hepatic sinusoidal obstruction syndrome (HSOS) induced by misuse of Gynura japonica has increased and gained global attention. Large amounts of pyrrolizidine alkaloids (PAs) are present in G. japonica; these PAs are metabolically activated to generate pyrrole-protein adducts (PPAs). In this study, male SD rats were treated orally with a single dose of G. japonica extract (GJE) at 0.062 5, 0.25, 0.5, 1, and 2 g·kg^-1. Blood was collected from the orbital venous plexus at 2, 12, 24 and 48 h, and at 48 h after treatment the rats were anesthetized with isoflurane and livers were collected for hematoxylin & eosin staining. The kinetics of PPAs at different doses were studied at 10, 20, 30 min, 1, 2, 4, 6, 12, 24 h, and 48 h, after a single gavage of GJE. The experimental scheme was approved by the ethics committee of animal experiments of Shanghai University of Traditional Chinese Medicine (PZSHUTCM190912019). The concentration of PPAs in serum was determined by liquid chromatography-mass spectrometry (LC-MS). Kinetic data were processed by using the non-compartmental pharmacokinetics data analysis software program PK solutions 2^TM. The results demonstrate that the concentration of PPAs increased with the dose of GJE and positively correlated with the severity of liver injury. The elimination rate of PPAs in rats was significantly prolonged at higher doses. The level of PPAs and their clearance rate may serve as useful references for the detoxification of PAs-induced injuries.

Traditional Chinese medicine (TCM) network pharmacology and molecular docking technology were applied to explore the mechanism of anti-coronavirus pneumonia (coronavirus disease 2019, COVID-19) of Qingfei Paidu decoction. The Chinese Pharmacopoeia (2015 edition) and Traditional Chinese Medicine Systems Pharmacology (TCMSP), OMIM (Online Mendelian Inheritance in Man), GeneCard, STRING, and others online databases are used for building a series of network, and selecting the core target and analyzing the signal pathway. Finally, we make molecular docking predictions for the important compounds. The results showed that the Qingfei Paidu decoction compound-pneumonia target network contained 292 compounds and 214 corresponding targets, and the core targets involved AKT1 (AKT serine/threonine kinase 1), IL6 (interleukin 6), MAPK8 (mitogen-activated protein kinase 8), MAPK1 (mitogen-activated protein kinase 1), and JUN (jun proto-oncogene). GO (Gene Ontology) function enrichment analysis yielded 858 GO entries, and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment screening yielded 122 related pathways, including hypoxia inducible factor-1 (HIF-1) and Toll-like receptor (TLRs) signaling pathways related to pneumonia, as well as T-cell receptor (TCR) signaling pathway related to lung injury protection. The molecular docking results showed that some core compounds of the Chinese herbal medicine of Qingfei Paidu decoction have a certain degree of affinity for 2019-novel coronavirus (2019-nCoV) main protease (3C-like protease, 3CLpro) and angiotensin-converting enzyme 2 (ACE2). In this paper, we preliminarily explored the potential therapeutic mechanism for Qingfei Paidu decoction to against COVID-19 and predicted the active ingredients. We hope that the results will help to the further study on the active ingredients and mechanism of Qingfei Paidu decoction to COVID-19.