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Release Date:2020/4/26 10:49:17

pick  Important: Purpose  Discussion on the prevention and treatment of covid-19 by huatangerine(COVID-19)Objective to provide a basis for the clinical application of huatangerine.method  Through literature review, the pharmacological effects of Huajuhong and its main chemical components in expectorant, anti acute lung injury, anti-inflammatory, anti pulmonary fibrosis, antitussive, antioxidant, anti liver injury and anti kidney injury were analyzed(TCMSP)And searching the literature to search the chemical components of huatangerine, and compare the chemical components with angiotensin converting enzyme(ACE2)、3CLHydrolase(Mpro)(PLP)And dendritic cell specific intercellular adhesion molecules-3Binding non integrin factors(DC-SIGN)Molecular docking was performed to predict its role in inhibiting covid-19(SARS-CoV-2).result  The results of literature analysis showed that Huajuhong and its main chemical components had many pharmacological activities, such as expectorant, anti acute lung injury, anti-inflammatory, anti pulmonary fibrosis, antitussive, antioxidant, anti liver injury and anti kidney injury; Molecular docking results showed that naringin(naringin)(neohesperdin), Picroside(rhoifolin), citrinin(poncirin)And sitoside(sitogluside)WithACE2、MPro、PLPandDC-SIGNBoth have strong binding force and inhibitSARS-CoV-2.conclusion  (COVID-19)The potential of the course of the disease, in turn, may act onACE2、MPro、PLPandDC-SIGNPlay a role in inhibiting the virus infection of host cells and self replication. It is suggested that orange peel may be beneficial to(COVID-19)The prevention and treatment of the disease has a positive effect.

 

 

 

2019(severe acute respiratorysyndrome coronavirus 2,SARS-CoV-2)Covid-19 pneumonia(COVID-19)At present, the epidemic situation is spreading rapidly, and the cumulative number of cases of covid-19 in the world has exceeded200Wan, a serious threat to human life and health.2020year3month12dayThe World Health Organization announced that the epidemic of covid-19 could be characterized as a pandemic.COVID-19The main symptoms at the time of onset are fever, cough, expectoration, dyspnea, chest pain, fatigue, loss of appetite, headache, myalgia, hemoptysis and diarrhea[1]Some patients also suffer from injury of tissues and organs such as myocardium, liver and kidney. The "diagnosis and treatment plan for covid-19 pneumonia (trial version 6)" issued by the National Health Commission and the State Administration of traditional Chinese medicine pointed out that this disease belongs to the category of "epidemic disease" in traditional Chinese medicine, and the cause of the disease is to feel the gas of "epidemic disease"; And formulated a detailed treatment plan of traditional Chinese medicine. In addition, relevant departments of more than 20 provinces, autonomous regions and municipalities directly under the central government organized expert groups according to the local actual situation and also formulated relevant TCM diagnosis and treatment plans. Although the understanding of the pathogenesis of the disease at all stages is not completely the same, a considerable number of views believe that the epidemic is mainly characterized by "dampness", and the disease location is mainly in the lung[2-3]。

Huajuhong is a Rutaceae plant Huazhou pomeloCitrus grandis ‘Tomentosa’Or pomeloCitrus grandis(L.) OsbeckThe immature or nearly mature dry outer peel is warm in nature, pungent and bitter in taste, and belongs to the lung and spleen meridians. It has the function of regulating qi, eliminating dampness and resolving phlegm. It is used for coughing with excessive phlegm, vomiting evil and stuffy[4]Huajuhong was once a tribute of the Ming and Qing Dynasties and one of the top ten Guangyao. According to the records of Huazhou in the Guangxu edition of the Qing Dynasty, "Huazhou orange is as good as God in treating phlegm, and each piece of it can be worth a gold.". according toCOVID-19The main symptoms (such as cough, expectoration, dyspnea, etc.), etiology and pathogenesis, and the traditional efficacy of Huajuhong. It is speculated that Huajuhong may play an important role in some syndrome typesCOVID-19Can play an active role in the prevention and control of. COVID-19For those with dampness toxin depressing lung syndrome, the recommended prescription includes huatangerine.

In order to fully understand the role of Huajuhong in modern medicineCOVID-19Through literature review, this paper intends to analyze the pharmacological effects of Huajuhong and its main chemical components in expectorant, anti acute lung injury, anti-inflammatory, anti pulmonary fibrosis, antitussive, antioxidant, anti liver injury and anti kidney injury, and use molecular docking method to compare the chemical components of Huajuhong withSARS-CoV-2Enter host cells and self replication related important protein angiotensin converting enzyme(ACE2)、3CLHydrolase(Mpro)(PLP)And dendritic cell specific intercellular adhesion molecules-3Binding non integrin factors(DC-SIGN)Virtual docking was carried out to predict the chemical constituents in Citrus grandiflora LSARS-CoV-2For the application of huatangerine inCOVID-19To provide references for the future of.

1  method

1.1  Literature collection and analysis

. Among them, the flavonoids are mainly naringin, naringenin, Picroside, etc[5]Coumarins are mainly coumarins and isoimperatorin, hesperidin hydrate and isohesperidin, etc[5]The volatile oils were mainly limonene andβ-Laurene et al[6]Naringin is the component measured under the "content determination" of huatangerine in Chinese Pharmacopoeia[4]In this study, "Huajuhong", "Huazhou pomelo", "naringin", "naringenin", "Picroside", "coumarin", "isoimperatorin", "hesperidin hydrate", "isohesperidin", "limonene" and“β-Myrcene "and other Chinese keywords were retrieved from CNKI(CNKI); With English keywords“Exocarpium Citri Grandis”“Citrusgrandis ‘Tomentosa’ ”“Citrus grandis (L.) Osbeck”“naringin”“naringenin”“Rhoifolin”“Coumarin”“Isoimperatorin”“Meranzin hydrate”“Isomeranzin”“Cinene”And“β-Myrcene”SearchPubmed, read and analyze the pharmacology research literature of expectorant, anti acute lung injury, anti-inflammatory, anti pulmonary fibrosis, antitussive, antioxidant, anti liver injury and anti kidney injury in detail.

1.2  molecular docking

According to the literature[7],SARS-CoV-2Is a spike glycoprotein expressed through(S-Protein) vsACE2Combine to enter host cells, and then induce disease. ,SARS-CoV-2OfS-Protein and human bodyACE2Binding affinity is much higher thanSARS-CoVOfS-Protein, which is the main reason for its strong infectivity[8]。DC-SIGNyesCOne of the main members of the type a lectin receptor, which can recognize the carbon chain structure of viral glycoprotein, plays an important role in virus capture, anchoring host cells and large-scale propagation in the human body; AndDC-SIGNExpressed on the surface of dendritic cells and able to synergizeACE2Receptors withpHDependency mode willSARS-CoVEndocytosed into cells, facilitating the entry of viruses into host cells[9]。SARS-CoV-2belong toRNAVirus, in the process of replication, first needs to encode a multimeric precursor protein, and then hydrolyze to produce a functional protein. This hydrolysis process is mainly composed ofMproparticipate in[10], therefore,SARS-CoV-2Of3CLHydrolases are potential targets for the treatment of covid-19. coronavirusPLPIt is one of the important proteases in coronavirus replication[10]In view of this, in this study, the chemical constituents in huatangerine were compared with the targetACE2、Mpro、LPLandDC-SIGNVirtual docking was performed to predict its role in inhibitingSARS-CoV-2Activity in viral infection and replication.

Through the traditional Chinese Medicine System Pharmacology platform(TCMSP,http://tcmspw.com/)After searching and consulting the literature, the chemical constituents of Citrus sinensis were obtained50Pieces (table1). fromPubChem(https://pubchem.ncbi.nlm.nih.gov)Downloaded from the databaseSDFFormat. stayDiscoverystudio 2016In the software toolbarMinimizeLigandsModule, click FullMinimization, batch applicationCHARMmForce field optimization of small molecule structure. fromRCSDProtein data bank(https://www. rcsb.org/)DownloadACE2(PDB ID:1R4L)、Mpro(PDB ID:6LU7)、LPL(PDB ID:4OVZ)AndDC-SIGN(PDB ID:6GHV)Crystal structure, inDiscovery studio 2016Water molecules with crystal structure were deleted from the software, andPrepare ProteinFunctional complementation of incomplete residues, hydrogenation, and distribution of related charges.ACE2、Mpro、PLPandDC-SIGNThe protoligands in the protein crystal complex structure areXX5、N3、P85andEZ8, is an inhibitor of the corresponding target protein, and has good binding activity with the target protein. The binding position of the original ligand inhibitor of each target was selected as the docking activity pocket. adoptLibDockThe module couples the small molecule and the protoligand into the corresponding protein structure active pocket, and the docking parameters are divided byConformation MethodSet toBESTIn addition, the default parameters are selected for other parameters, and the docking results with higher scores are retained, and the docking results of the original ligand are used as a reference.

2  Results and analysis

2.1  Literature analysis of the pharmacological effects of Huajuhong and its main chemical components

2.1.1  Expectorant effect The gross observation report on the autopsy of patients with new coronal pneumonia showed that a large number of viscous secretions could be seen on the cut surface of the lungs overflowing from the alveoli, white foamy mucus could be seen in the tracheal cavity, and jelly like mucus could be seen in the lumen of the right pulmonary branch[11]It can be seen that a large amount of mucin is secreted in the lungs of severe patients with covid-19.

According to the records of Huazhou published by Guangxu in the Qing Dynasty, "Huazhou orange is as good as God in treating phlegm". Many modern pharmacological studies have reported the expectorant effect of huatangerine and its chemical components.Jiangetc.[12]According to our research, huatangerine70%Ethanol extract can significantly promote phenol red excretion in mouse airway; Lipeibo et al[13]The study showed that Huazhou pomelo flavonoid extract could promote the excretion of phenol red in the airway of mice and increase the amount of sputum excretion in the glass tube of rats.Chenetc.[14]Using lipopolysaccharide(LPS)Induction of mice andBeagleThe expectorant effect of naringin was investigated in a canine model of acute lung injury. The results showed that naringin could inhibit the proliferation of airway goblet cells and mucin 5AC(MUC5AC); Further mechanism study showed that naringin inhibited mucin secretion may be related to its inhibition of mitogen activated kinase/Activator protein-1(MAPKs/AP-1)AndIKKs/IκB/nuclear factorκB(NF-κB)Signaling pathway[15]。Linetc.[16]The results showed that naringenin could not only increase the secretion of phenol red in the airway of mice, but also improve the transport capacity and inhibition of airway ciliaLPS.Yangetc.[17](EGFR)-Phosphatidylinositol3-Kinases(PI3K)-protein kinaseB(Akt)/Extracellular signal regulated protein kinase(ERK)/MAPKSignaling pathway inhibits human neutrophil elastase induced airway epithelial cell generationMUC5AC。Shietc.[18](cAMP)Content, which in turn increases the cystic fibrosis transmembrane conductance regulator(CFTR)It can promote chloride ion secretion and ultimately increase the secretion of airway serous fluid. It can be seen that huatangerine and its main chemical components naringin and naringenin can both inhibitMUC5ACIt can also promote the secretion of serous fluid to dilute sputum, and promote the movement of airway cilia, which has a significant expectorant effect.

2.1.2  Anti acute lung injury effect  Acute lung injury(ALI)/Acute respiratory distress syndrome(ARDS)It is a common clinical critical illness, which seriously threatens the life of critically ill patients and has a very high mortality. In severe and critically ill patients with covid-19,ALI/ARDSIt is one of the important causes of respiratory failure.

Liuetc.[19]adoptLPSThe effects of naringin on acute lung injury in mice were studied. The results showed that oral administration of naringin could significantly reduce pulmonary edema, lung tissue structural damage and neutrophil infiltration, and inhibit myeloperoxidase in lung tissue(MPO)And inducible nitric oxide synthase(iNOS)Activity and tumor necrosis factor-α(TNF-α)Secretion of.Chenetc.[14, 20]The study of naringin showed that naringin could significantly reduceLPSInduction of pulmonary edema, structural damage of lung tissue and inflammatory cell infiltration in acute lung injury model dogs andTNF-αAnd interleukin-8(IL-8)It can also significantly reduce the death of mice with acute lung injury induced by paraquat, and significantly inhibit the infiltration of inflammatory cells in the lungs andTNF-αTransforming growth factorβ1(TGF-β1)Generation of.Zhaoetc.[21]adoptLPSInduction of acute lung injury mouse model the effect of naringenin was studied. The results showed that oral administration of naringenin could improve the survival rate of model mice, improve the pathological changes of lung tissue, reduce pulmonary edema and pulmonary vascular leakage, reduce neutrophil infiltration, and reduce the inflammatory cytokines in serum and lung bubble lavage fluidTNF-α, interleukin1β(IL-1β), interleukin6(IL-6)And macrophage inflammatory proteins2(MIP-2)The mechanism of action may be related to the inhibition ofPI3K/AKTSignaling pathway.Fouadetc.[22]adoptLPS The effect of naringenin was studied in a rat model of induced acute lung injury. The results showed that naringenin could significantly inhibit neutrophil recruitment and inflammatory cytokines in the lungTNF-α、IL-6To reduce lung tissue damage, alveolar wall thickening, interstitial edema. LPSThe acute lung injury caused by has a significant inhibitory effect.

2.1.3  anti-inflammatory effect Inflammatory storm (cytokine storm) is an excessive immune response caused by the positive feedback cycle between cytokines and immune cells caused by infection, drugs or some diseases. 2(IL-2), interleukin7(IL-7), interleukin10(IL-10), granulocyte-Macrophage colony stimulating factor(GM-CSF), interferon inducible protein-10(IP-10), monocyte chemoattractant protein-1(MCP-1)Macrophage inflammatory protein1α(MIP-1α)、IL-6andTNF-α[23]。

There are many literature reports on the anti-inflammatory effects of Huajuhong and its chemical components naringin, naringenin and wild rhubarb glycoside. Studies have shown that huatangerine70%Ethanol extract[12]Huazhou orange polysaccharide[24]Both can inhibit xylene induced mouse auricle swelling and have obvious anti-inflammatory effect. Huatangerine polysaccharide also has a significant anti-inflammatory effect on the inflammatory response of chronic pharyngitis patients and experimental chronic pharyngitis model rabbits[25]The total flavonoids of Citrus sinensis can regulateMAPKandNF-κBSignaling pathway inhibitionLPSinduceRAW264.7Cell productionTNF-α, interleukin1β(IL-1β)AndIL-6[26]. xierenfeng et al[27]The anti-inflammatory effect of naringin was observed by using the experimental model of xylene induced acute ear swelling and peritoneal capillary permeability. The results showed that naringin had significant anti-inflammatory effect, and its mechanism may be related to the inhibition of inflammatory tissue prostaglandinsE2(PGE2)Related to the synthesis or release of.Kannoetc.[28]The study of naringin showed that naringin could significantly reduceLPSThe death of endotoxic shock induced mice can be significantly reducedLPSinduceRAW 264.7CellulariNOS、TNF-α, cyclooxygenase2(COX-2)AndIL-6OfmRNAExpression.Kawaguchietc.[29]The study showed that naringin had a significant protective effect on the endotoxin shock model mice infected by Salmonella, could reduce the mortality of mice, and inhibited theTNF-αGeneration of.Giletc.[30]Naringin can significantly inhibit the lung inflammation induced by cecal ligation and perforation in septic mice andLPSinduceRAW 264.7Cell productionTNF-αAnd high mobility group proteinsB1(HMGB1)。Liuetc.[31]The results showed that naringin could inhibit theLPSinduceRAW 264.7Cells release inflammatory cytokinesIL-8、MCP-1andMIP-1α, the mechanism may be related to inhibitionNF-κBandMAPK. Other studies have shown that naringin can significantly inhibit chronic smoking induced rats[32]And guinea pigs[33]Chronic inflammation of the respiratory system. Wuwenwei et al[34]Naringenin was found to significantly reduce the lung tissue of Staphylococcus aureus pneumonia model miceIL-6、IL-1βandTNF-α.Jinetc.[35]The results showed that naringenin could inhibitLPSinduceRAW 264.7Cells andTCells release inflammatory cytokinesTNF-αandIL-6The mechanism is related to the regulation of lysosomal function to promote the degradation of cytokines in the cell.Liuetc.[36]It was found that naringenin can activate transcription through3(ATF3)-Signaling transcriptional activators3(STAT3)DependenceNegative regulationLPS/TollLike receptor4(TLR4)Signaling pathway to protect endotoxemia mice and inhibitLPSinduceRAW264.7Cell productionTNF-α、IL-6、TLR4、iNOS、COX2andNADPHoxidase2(NOX2)Et al.Yuetc.[37]adoptLPSThe anti-inflammatory effect of naringenin was studied in an in vitro model of inducing inflammatory injury of bronchial epithelial cells. The results showed that naringenin could inhibitMAPKandNF-κBSignaling pathway reductionTNF-αandIL-6Generation of. Other studies have shown that naringenin has a significant effect onLPSInduction of microglia[38], cardiomyocytes[39], nerve cells[40]. In addition, songxiaoxin et al[41]The study showed that vernicidin could inhibitLPSCaused byRAW 264.7Cellular inflammatory response, reducing nitric oxide(NO)Secretion, inhibitionTNF-α、IL-1βandIL-6OfmRNAExpression, inhibitionc-Jun(JNK)/Stress activated protein kinase(SAPK)AndERKSignaling pathway may be one of its anti-inflammatory mechanisms;de Souzaetc.[42]Our study showed that limonene can inhibit the gastric tissue of rats with ethanol induced gastric ulcerTNF-α、IL-6andIL-1β. In conclusion, huatangerine and its multiple chemical components have anti-inflammatory effects.

2.1.4  Cough suppression  Cough is one of the main symptoms of covid-19. . Modern pharmacological studies have shown that huatangerine and its various chemical components have significant antitussive effects on experimental cough animal models.Jiangetc.[12]According to our research, huatangerine70%The ethanol extract had significant inhibitory effect on ammonia induced cough in mice; Many studies of lipeibo's research group showed that the flavonoid extract of Huazhou pomelo[43]And naringin[44]All of them could significantly inhibit the cough induced by capsaicin in guinea pigs, and the antitussive mode was not central antitussive; Naringenin also has inhibitory effect on ammonia induced cough in mice[45]In addition, studies have also shown that,MeliditinIt can inhibit the cough of guinea pigs caused by citric acid[46]。

2.1.5  Anti pulmonary fibrosis  Pulmonary fibrosis is a lung disease characterized by the injury and abnormal proliferation of alveolar epithelial cells, the deposition of extracellular matrix and the proliferation and activation of fibroblasts. Because it can lead to the destruction of lung structure and the loss of respiratory function, the prognosis of pulmonary fibrosis is poor. Severe respiratory viral pneumonia (e.gSARS, covid-19) have a high probability of developing pulmonary fibrosis. [47]The rat model of pulmonary fibrosis was established by intratracheal instillation of bleomycin, and the effect of Huajuhong decoction was investigated. The results showed that Huajuhong decoction could inhibit basic fibroblast growth factor in rats with pulmonary fibrosis by inhibiting(bFGF)Expression and promotion of platelet4Factor(PF4)Expression and inhibit angiogenesis, thereby inhibiting the progression of idiopathic pulmonary fibrosis.Turgutetc.[48]The rat model of pulmonary fibrosis induced by bleomycin was also used to investigate the effect of oral administration of naringin. The results showed that naringin could significantly reduce the lung injury of pulmonary fibrosis ratsTNF-α、IL-1β(HYP)(MDA)Levels, increasing glutathione peroxidase(GSH-Px)And superoxide dismutase(SOD).Chenetc.[20]Naringin can significantly reduce the lung tissue of paraquat induced pulmonary fibrosis model miceTNF-α、TGF-β1, matrix metalloproteinases(MMP-9)Tissue metalloproteinase inhibitor-1(TIMP-1)、HYPandMDAAnd significantly increased antioxidant enzymesSOD、GSH-PxAnd heme oxygenase1(HO-1)These results suggest that naringin has inhibitory effect on paraquat induced murine pulmonary fibrosis.

2.1.6  Antioxidant effect  Oxidative stress reaction plays an important role in the occurrence and development of a variety of pneumonia. Most viral infections trigger cellular oxidative stress. High dose vitaminsCClinical trials for the treatment of covid-19 have been conducted in the United StatesClnicaltrials.govRegister on the website[49]There are many reports on the antioxidant effects of huatangerine and its chemical constituents. Exocarpine polysaccharide has the ability of in vitro scavenging1,1-Diphenylpicryl phenyl hydrazine(DPPH)Ability of free radical, hydroxyl radical and superoxide anion radical[50]And increasing the level of IL-6 in the spleen of mice with immune injury induced by cyclophosphamideSODAnd glutathione(GSH)The activity and the reduction of serumMDAEffect of the content of[51]。Zhuetc.[52]The study showed that total flavonoids of Citrus grandiflora could significantly inhibitPM2.5Mouse lungs caused byMDAandNOIncrease in contentGSH-PxActivity andGSH/Oxidized glutathione(GSSG)It has the effect of anti oxidative damage. In vitro experiments have shown that naringin has significant hydroxyl radical, superoxide anion radical andDPPHScavenging activity[53-54]The significant antioxidant activity of naringenin is considered to be one of the important mechanisms for its prevention and treatment of cardiovascular disease, diabetes, neurodegenerative disease, respiratory disease, cancer, and kidney disease[55]. in addition,Bacanlıetc.[56]adoptTEACThe effect of limonene was studied by the method, and the results showed that the concentration range was2~2 000μmol/LLimonene has significant antioxidant activity in vitro.

2.1.7  other Clinically, there are a large number ofCOVID-19Patients will show the phenomenon of damage to other organs besides respiratory symptoms. Wangshuhui et al[57]right333The medical records of cases were retrospectively analyzed,39.6%(132/333)OfCOVID-19The patient developed liver injury;Huangetc.[23]Of the article showed that part ofCOVID-19There were acute myocardial injury and renal damage in the infected patients. A large number of studies have shown that naringin can inhibit oxidative stress, prevent transdifferentiation of hepatic stellate cells, and inhibitMAPK、TLRandTGF-βSignaling pathway plays a role in protecting the liver[58], including inhibiting hepatotoxicity caused by drugs and chemical toxins[59]In addition, animal experiments have shown that naringin can prevent acute renal failure induced by glycerol in rats[60]Iron nitrilotriacetateOxidative kidney injury in rats[61]Sepsis induced acute kidney injury in rats[62]Both have protective effects; Effects of naringenin on adriamycin induced renal toxicity in rats[63]Renal damage in diabetic nephropathy rats[64]Carbon tetrachloride induced acute nephrotoxicity in mice[65]. In addition, it has been reported that naringin has acute cardiotoxicity induced by doxorubicin in rats[66], lipopolysaccharide induced myocardial injury in mice[67], isoproterenol induced myocardial infarction in rats have inhibitory effects[68]Effects of naringenin on myocardial injury induced by myocardial ischemia-reperfusion in rats[69]And doxorubicin induced cardiotoxicity in rats[70]It also has inhibitory effect. It can be seen that naringin and naringenin, the main flavonoids in huatangerine, have protective effects on myocardial, liver and kidney damage.

2.2  Analysis of molecular docking results

surface2The chemical components of Citrus grandiflora were listed before docking and scoring with each target10. The components in Huajuhong andACE2The docking results showed that neohesperidin(neohesperdin), naringin(naringin)And citrinin(poncirin)The highest score was given to all of them, which were higher than that of the original ligand(XX5)Score of; WithMproThe docking results of Picroside showed that(rhoifolin); WithPLP; WithDC-SIGNThe docking results showed that citrin, naringin and neohesperidin scored the highest. The interactions between some representative active ingredients and target proteins are shown in Fig1~2(sitogluside)WithACE2、MPro、PLPandDC-SIGNBoth of them have strong binding force and are the most important5Active ingredients (Fig3), suggesting that it has inhibitorySARS-CoV-2.

3  discuss

SARS-CoV-2Widespread worldwide dissemination andCOVID-19The outbreak of is a serious threat to human health. At present, there is no specific vaccine and therapeutic drug in the world. According to the diagnosis and treatment plan for covid-19 pneumonia (trial version 7),COVID-19The pathological changes were mainly in the lungs, but multiple organs were involved; The main symptoms are fever, dry cough, fatigue, and severe cases can rapidly progress to acute respiratory distress syndrome, septic shock, and multiple organ failure. Through the literature review and analysis of the pharmacological effects of Huajuhong and its main chemical components, it was found that Huajuhong and its main chemical components, especially naringin and naringenin, have many pharmacological activities, such as expectorant, anti acute lung injury, anti-inflammatory and so on. In terms of expectorant, according to the record of "Materia Medica from new", Huazhou orange peel is very effective in eliminating phlegm; MUC5ACAnd can promote the secretion of serous fluid, suggesting its effect onCOVID-19. According to some studies,IL-6Levels were higher in critically ill patients,COVID-19CirculatingIL-6Can be predicted independentlyCOVID-19The course and prognosis of[71]At present, there are clinical trials(ChiCTR2000029765)Evaluation in progressIL-6The receptor blocker tocilizumab inCOVID-19Effectiveness and safety in[72]According to the diagnosis and treatment plan for pneumonia caused by covid-19 (trial version 7), for severe patients and laboratory testsIL-6Patients with elevated levels are recommended to try tocilizumab. Studies in multiple cell and animal models have shown that huatangerine and its main chemical components can significantly inhibit inflammatory cytokinesIL-6、TNF-α、IL-1βIt may play an active role in the prevention and treatment of lung inflammation and inflammatory storm. In addition, huatangerine and its main chemical components can also inhibit myocardial injury, liver and kidney damage pulmonary fibrosis、 . It is suggested that Huajuhong can play an active role in the prevention and treatment of new coronal pneumonia.

ACE2、MPro、PLPandDC-SIGNyesSARS-CoV-2Key proteins that infect host cells or self replicate and are considered anti -SARS-CoV-2Important targets for drug screening. This study showed that naringin, neohesperidin, anacardin, citrinin, and sitoside in Huajuhong have strong binding ability with these potential target proteins, and play an important role in inhibitingSARS-CoV-2It may have potential activity in infecting host cells or self replication. Studies have shown that[73]Naringenin can inhibit Zika virus infection by interfering with virus replication or the assembly of virus particlesA549Cells and primary human monocyte derived dendritic cells.Frabasileetc.[74]The study showed that naringenin could inhibit the growth of dengue virus inHuh7.5Replication in cells and primary human monocytes.

To sum up, based on the literature analysis and molecular docking study, this study believes that Huajuhong has the potential to prevent acute lung injury through its expectorant, anti-inflammatory, anti pulmonary fibrosis, antitussive, antioxidant, anti liver injury, anti kidney injury and antiSARS-CoV-2And other pharmacological activitiesCOVID-19The role of. This study is to develop the anti-virus activity of Huajuhong.The anti-virus activity of Huajuhong against the anti-virus of Citrus sinensis in vitro..the anti-virus activity of Huajuhong was investigated...The anti-virus activity of HuajuhongCOVID-19The further pharmacodynamic and clinical efficacy experimental research and the research and development of related new drugs provide a scientific basis.

References (omitted)  

References (omitted)   ; Pan, Wu   Hao, wangyonggang, raohongyu, Su Weiwei Based on the literature analysis and molecular docking method, this paper discusses the prospect of orange red for the prevention and treatment of covid-19 [j]. Chinese herbal medicine, 2020, 51 (9): CNKI first
 

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