1.Frequently Used Allopathic and Traditional Medicine for COVID-19 Treatment and Feasibility of Their Integration.
Aditya UPADHAYAY ; Gopal PATEL ; Dharm PAL ; Awanish KUMAR
Chinese journal of integrative medicine 2022;28(11):1040-1047
To date, no satisfactory treatment for COVID-19 is available. This review reported few recent updates regarding the drugs (allopathy/traditional medicines) used for the treatment of COVID-19 concerning clinical studies. Content of the article spotlight the contribution of allopathic and Ayurvedic drugs to the scientific basis for utilization as a potential therapy against COVID-19 infection and provide new insights on the integration of allopathy and traditional medicine. It advocated the combination of these two systems of treatment will ascertain their integrations, and there would be a good possibility and scope for developing a model of integration in the management of COVID-19. Provided discussion may help researchers, physicians, and healthcare policymakers to encourage for effective and integrated use of allopathic and Ayurvedic medicines to control the COVID-19 pandemic more effectively.
Humans
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Feasibility Studies
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Pandemics
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Medicine, Traditional
;
COVID-19 Drug Treatment
2.Potential medicinal plants involved in inhibiting 3CLpro activity: A practical alternate approach to combating COVID-19.
Fan YANG ; Xiao-Lan JIANG ; Akash TARIQ ; Sehrish SADIA ; Zeeshan AHMED ; Jordi SARDANS ; Muhammad ALEEM ; Riaz ULLAH ; Rainer W BUSSMANN
Journal of Integrative Medicine 2022;20(6):488-496
At present, a variety of vaccines have been approved, and existing antiviral drugs are being tested to find an effective treatment for coronavirus disease 2019 (COVID-19). However, no standardized treatment has yet been approved by the World Health Organization. The virally encoded chymotrypsin-like protease (3CLpro) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which facilitates the replication of SARS-CoV in the host cells, is one potential pharmacological target for the development of anti-SARS drugs. Online search engines, such as Web of Science, Google Scholar, Scopus and PubMed, were used to retrieve data on the traditional uses of medicinal plants and their inhibitory effects against the SARS-CoV 3CLpro. Various pure compounds, including polyphenols, terpenoids, chalcones, alkaloids, biflavonoids, flavanones, anthraquinones and glycosides, have shown potent inhibition of SARS-CoV-2 3CLpro activity with 50% inhibitory concentration (IC50) values ranging from 2-44 µg/mL. Interestingly, most of these active compounds, including xanthoangelol E (isolated from Angelica keiskei), dieckol 1 (isolated from Ecklonia cava), amentoflavone (isolated from Torreya nucifera), celastrol, pristimerin, tingenone and iguesterin (isolated from Tripterygium regelii), tannic acid (isolated from Camellia sinensis), and theaflavin-3,3'-digallate, 3-isotheaflav1in-3 gallate and dihydrotanshinone I (isolated from Salvia miltiorrhiza), had IC50 values of less than 15 µg/mL. Kinetic mechanistic studies of several active compounds revealed that their mode of inhibition was dose-dependent and competitive, with Ki values ranging from 2.4-43.8 μmol/L. Given the significance of plant-based compounds and the many promising results obtained, there is still need to explore the phytochemical and mechanistic potentials of plants and their products. These medicinal plants could serve as an effective inexpensive nutraceutical for the general public to help manage COVID-19.
SARS-CoV-2
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Plants, Medicinal
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COVID-19 Drug Treatment
3.Medication Rule Analysis of the Diagnosis and Treatment Programs of Chinese Medicine for the Prevention and Treatment of COVID-19 in China.
Xin-Yu JI ; Yan MA ; Shuai SHI ; Si-Hong LIU ; Lin TONG ; Cheng LYU ; Hua-Min ZHANG ; Yan-Ping WANG
Chinese journal of integrative medicine 2022;28(9):779-784
OBJECTIVES:
To summarize the measures and rules of Chinese medicine (CM) and provide reference for clinical application in the prevention and treatment of coronavirus disease (COVID-19).
METHODS:
The data source was from CM COVID-19 prevention and treatment programs on government websites and official media websites of the different provinces and cities. The search lasted from December 8, 2019 to March 10, 2020. Main variables were medication frequency and combinations of medicines. Cluster analysis and complex network analysis were used by prevention and treatment stage and by area.
RESULTS:
Among 27 CM diagnosis and treatment plans, 203 therapeutic prescriptions were enrolled, of which the top 4 herbs were: Radix glycyrrhizae, Semen armeniacae amarum, Herba ephedrae, and Herba agastachis, respectively. The core combinations were Herba ephedrae and Semen armeniacae amarum. Forty-eight preventive formulae were identified. Ten herbs, including Radix Astragali seu hedysari, Radix glycyrrhizae, Radix saposhnikoviae, Flos lonicerae, etc. were most frequently used. The core prescription of CM compatibility was Radix astragali seu hedysari, Radix glycyrrhizae, and Radix saposhnikoviae, which is the main component of Yu Ping Feng San. There were 45 prevention and treatment prescriptions in East China; the most used CM was Radix glycyrrhizae, Herba agastachis, Pericarpium citri reticulatae, and Gypsum fibrosum. Fifty prescriptions were identified in North China. According to CM analyses, Herba agastachis, Semen armeniacae amarum, Herba ephedrae, and Poria were most frequently used.
CONCLUSIONS
CM for COVID-19 prevention mainly focuses on improving human immunity; for treatment, prescription focuses on clearing the lungs and removing dampness. Prescriptions vary with regions, perhaps due to climatic and environmental differences, which help clinicians to quickly make CM plans and treat patients according to clinical status, further minimizing resource wastage.
COVID-19/diagnosis*
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COVID-19 Testing
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China/epidemiology*
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Drugs, Chinese Herbal/therapeutic use*
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Humans
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Medicine, Chinese Traditional
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COVID-19 Drug Treatment
4.Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial.
Dongsheng WANG ; Binqing FU ; Zhen PENG ; Dongliang YANG ; Mingfeng HAN ; Min LI ; Yun YANG ; Tianjun YANG ; Liangye SUN ; Wei LI ; Wei SHI ; Xin YAO ; Yan MA ; Fei XU ; Xiaojing WANG ; Jun CHEN ; Daqing XIA ; Yubei SUN ; Lin DONG ; Jumei WANG ; Xiaoyu ZHU ; Min ZHANG ; Yonggang ZHOU ; Aijun PAN ; Xiaowen HU ; Xiaodong MEI ; Haiming WEI ; Xiaoling XU
Frontiers of Medicine 2021;15(3):486-494
Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.
Antibodies, Monoclonal, Humanized
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COVID-19/drug therapy*
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Humans
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SARS-CoV-2
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Treatment Outcome
5.COVID-19 treated with oral Nirmatrelvir-Ritonavir in 3 children.
Shuang SHI ; Na DONG ; Ying DING ; Chao WANG ; Lang YUAN ; Yong Shuang FANG ; Bing Jie WANG ; Yan Hua NIU ; Zhen Zhen WEI ; Tian PU ; Xiao Yan DONG ; Quan LU
Chinese Journal of Pediatrics 2022;60(11):1168-1171
Objective: To summarize the application experience and the therapeutic effect of Nirmatrelvir-Ritonavir (trade name: Paxlovid) for COVID-19 in children. Methods: A retrospective analysis was performed on the clinical data, including collecting the clinical manifestations and clinical outcomes, dynamically monitoring the blood routine, hepatic and renal function and SARS-CoV-2 nucleic acid results, and observing the related side effects during the treatment, etc, of 3 cases with COVID-19 treated with Paxlovid admitted to Shanghai Children's Hospital (designated referral hospital for SARS-CoV-2 infection in Shanghai) from May 1st to June 1st, 2022. Results: The 3 cases were 12, 14, 17 years of age, among which 2 cases were males, 1 case was female. All 3 cases were mild cases with underlying diseases and risk of developing into severe COVID-19, with symptoms of high fever, sore throat and dry cough. The treatment of Paxlovid at 3rd day of symptom onset contributed to the symptom-free after 1-2 days and negative results of SARS-CoV-2 nucleic acid after 2-4 days. All patients had no adverse manifestations of gastrointestinal tract and nervous system but a case had little skin rashes, which recovered after the withdrawal of Paxlovid. Three cases had normal hepatic and renal function during the Paxlovid treatment. At 3 months after discharge, no clinical manifestations of post-COVID syndrome were found in all 3 cases. Conclusion: Paxlovid was effective and relatively safe in the treatment of 3 children with COVID-19.
Child
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Male
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Humans
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Female
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COVID-19
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SARS-CoV-2
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Ritonavir/therapeutic use*
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Retrospective Studies
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China
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Nucleic Acids
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COVID-19 Drug Treatment
6.Methodology of network pharmacology for research on Chinese herbal medicine against COVID-19: A review.
Yi-Xuan WANG ; Zhen YANG ; Wen-Xiao WANG ; Yu-Xi HUANG ; Qiao ZHANG ; Jia-Jia LI ; Yu-Ping TANG ; Shi-Jun YUE
Journal of Integrative Medicine 2022;20(6):477-487
Traditional Chinese medicine, as a complementary and alternative medicine, has been practiced for thousands of years in China and possesses remarkable clinical efficacy. Thus, systematic analysis and examination of the mechanistic links between Chinese herbal medicine (CHM) and the complex human body can benefit contemporary understandings by carrying out qualitative and quantitative analysis. With increasing attention, the approach of network pharmacology has begun to unveil the mystery of CHM by constructing the heterogeneous network relationship of "herb-compound-target-pathway," which corresponds to the holistic mechanisms of CHM. By integrating computational techniques into network pharmacology, the efficiency and accuracy of active compound screening and target fishing have been improved at an unprecedented pace. This review dissects the core innovations to the network pharmacology approach that were developed in the years since 2015 and highlights how this tool has been applied to understanding the coronavirus disease 2019 and refining the clinical use of CHM to combat it.
Humans
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Drugs, Chinese Herbal/therapeutic use*
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Network Pharmacology
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Medicine, Chinese Traditional/methods*
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Treatment Outcome
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COVID-19 Drug Treatment
8.Comparison of quality of life and long-term outcomes following mitral valve replacement through robotically assisted versus median sternotomy approach.
Haizhi ZHAO ; Huajun ZHANG ; Ming YANG ; Cangsong XIAO ; Yao WANG ; Changqing GAO ; Rong WANG
Journal of Southern Medical University 2020;40(11):1557-1563
OBJECTIVE:
To compare the mid- and long-term outcomes of patients receiving mitral valve replacement through robotically assisted and conventional median sternotomy approach.
METHODS:
The data of 47 patients who underwent da Vinci robotic mitral valve replacement in our hospital between January, 2007 and December, 2015 were collected retrospectively (robotic group). From a total of 286 patients undergoing mitral valve replacement through the median thoracotomy approach between March, 2002 and June, 2014, 47 patients were selected as the median sternotomy group for matching with the robotic group at a 1:1 ratio. The perioperative data and follow-up data of the patients were collected, and the quality of life (QOL) of the patients at 30 days and 6 months was evaluated using the Quality of Life Short Form Survey (SF-12). The time of returning to work postoperatively and the patients' satisfaction with the surgical incision were compared between the two groups.
RESULTS:
All the patients in both groups completed mitral valve replacement successfully, and no death occurred during the operation. In the robotic group, only one patient experienced postoperative complication (pleural effusion); in median sternotomy group, one patient received a secondary thoracotomy for management of bleeding resulting from excessive postoperative drainage, and one patient died of septic shock after the operation. The volume of postoperative drainage, postoperative monitoring time, ventilation time, and postoperative hospital stay were significantly smaller or shorter in the robotic group than in the thoracotomy group (
CONCLUSIONS
Robotically assisted mitral valve replacement is safe and reliable. Compared with the median sternotomy approach, the robotic approach is less invasive and promotes faster postoperative recovery of the patients, who have better satisfaction with the quality of life and wound recovery.
COVID-19/drug therapy*
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Humans
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Mitral Valve/surgery*
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Quality of Life
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Retrospective Studies
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Robotic Surgical Procedures
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Sternotomy
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Thoracotomy
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Treatment Outcome
9.Targeting papain-like protease for broad-spectrum coronavirus inhibition.
Shuofeng YUAN ; Xiaopan GAO ; Kaiming TANG ; Jian-Piao CAI ; Menglong HU ; Peng LUO ; Lei WEN ; Zi-Wei YE ; Cuiting LUO ; Jessica Oi-Ling TSANG ; Chris Chun-Yiu CHAN ; Yaoqiang HUANG ; Jianli CAO ; Ronghui LIANG ; Zhenzhi QIN ; Bo QIN ; Feifei YIN ; Hin CHU ; Dong-Yan JIN ; Ren SUN ; Jasper Fuk-Woo CHAN ; Sheng CUI ; Kwok-Yung YUEN
Protein & Cell 2022;13(12):940-953
The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals
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Coronavirus Papain-Like Proteases/antagonists & inhibitors*
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Cricetinae
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Humans
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Mice
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Pandemics
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SARS-CoV-2/enzymology*
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COVID-19 Drug Treatment
10.Analysis of mechanisms of Shenhuang Granule in treating severe COVID-19 based on network pharmacology and molecular docking.
Xiang-Ru XU ; Wen ZHANG ; Xin-Xin WU ; Hong-Qiang YANG ; Yu-Ting SUN ; Yu-Ting PU ; Bei WANG ; Wei PENG ; Li-Hua SUN ; Quan GUO ; Shuang ZHOU ; Bang-Jiang FANG
Journal of Integrative Medicine 2022;20(6):561-574
OBJECTIVE:
Severe cases of coronavirus disease 2019 (COVID-19) are expected to have a worse prognosis than mild cases. Shenhuang Granule (SHG) has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial, but the active chemical constituents and underlying mechanisms of action remain unknown. The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19, using network pharmacology.
METHODS:
Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG. Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform, SwissTargetPrediction, and Gene Expression Omnibus (GEO) databases. The target protein-protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms. Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets.
RESULTS:
Forty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets, including hub genes such as HSP90AA1, MMP9, CXCL8, PTGS2, IFNG, DNMT1, TYMS, MDM2, HDAC3 and ABCB1. Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction, calcium signaling pathway and cAMP signaling pathway. Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets. Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase.
CONCLUSION
Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways; this provides a scientific basis for clinical applications and further experiments.
Humans
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Molecular Docking Simulation
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Ligands
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Network Pharmacology
;
Drugs, Chinese Herbal/chemistry*
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Medicine, Chinese Traditional
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COVID-19 Drug Treatment