Potential mechanism of Xuanfei Baidu Formula in treating new coronavirus pneumonia based on network pharmacology and molecular docking

Objective:To investigate the molecular mechanism of antiviral effect of Xuanfei Baidu Formula in the treatment of coronavirus disease 2019(COVID-19),and to provide reference for the twreatment of COVID-19 with traditional Chinese medicine.Methods:Traditional Chinese Medicine Systems Pharmacology(TCMSP)was employed to search the effective active component and targets of Xuanfei Baidu Formula.Databases,GeneCards etc.were employed to obtain the relevant target genes of COVID-19 and intersect with the targets of Xuanfei Baidu Formula to obtain the therapeutic targets.The therapeutic targets were uploaded to the STRING database to obtain protein interaction(PPI)information,and Cytoscape was utilized to construct drug-target-disease networks,high-confidence PPI networks for target proteins,and active-target-pathway networks.GO,gene ontology,functional analysis and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis of potential targets of action were performed using the R package in Bioconductor.The main active components were molecular docking technology with 3C-like protease(3CLPro)and angiotensin-cinverting enzyme2(ACE2)and key targets of SARS-CoV-2,respectively.Results:A total of 99 effective active ingredients of Xuanfei Baidu Formula were selected,of which 22 active ingredients acting on COVID-19 could act on COVID-19 through 52 potential targets.Enrichment yielded 1,364 biological process entries and 22 KEGG pathways in GO,involving paths such as IL-17,JAK-STAT,MAPK,NF-κB,PI3K-Akt,Th1 and Th2 cell differentiation,Th17 cell differentiation,T cell receptor,vascular endothelial growth factor(VEGF)and Salmonella infection.Molecular docking technology results revealed that active components such as luteolin,beta-sitostero,formononetin,and shinpterocarpin in Xuanfei Baidu Formula embraced satisfactory binding to 3CLPro and ACE2,and also had good binding to core targets.Conclusion:Xuanfei Baidu Formula inhibits viral invasion and viral replication mainly by binding to ACE2 and 3CLPro receptors of SARS-CoV-2 through flavonoids and phytosterols,and may play a role in the treatment of COVID-19 by regulating key targets such as IL6,MAPK3,MAPK1,IL1β,CCL2,EGFR,and NOS2 after virus infection of cells,exerting anti-cytokine storm,anti-oxidation,and regulating the body's immunity.

New insights for infection mechanism and potential targets of COVID-19:Three Chinese patent medicines and three Chinese medicine formulas as promising therapeutic approaches

The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)with high pathogenicity and infectiousness has become a sudden and lethal pandemic worldwide.Currently,there is no accepted specific drug for COVID-19 treatment.Therefore,it is extremely urgent to clarify the pathogenic mechanism and develop effective therapies for patients with COVID-19.According to several reliable reports from China,traditional Chinese medicine(TCM),especially for three Chinese patent medicines and three Chinese medicine formulas,has been demonstrated to effectively alleviate the symptoms of COVID-19 either used alone or in combination with Western medicines.In this review,we systematically summarized and analyzed the pathogenesis of COVID-19,the detailed clinical practice,active ingredients investigation,network pharmacology prediction and underlying mechanism verification of three Chinese patent medicines and three Chinese medicine formulas in the COVID-19 combat.Additionally,we summarized some promising and high-frequency drugs of these prescriptions and discussed their regulatory mechanism,which provides guidance for the development of new drugs against COVID-19.Collectively,by addressing critical challenges,for example,unclear targets and complicated active ingredients of these medicines and formulas,we believe that TCM will represent promising and efficient strategies for curing COVID-19 and related pandemics.

基于网络药理学和分子对接探讨宣肺败毒方治疗新型冠状病毒肺炎的潜在作用机制

目的:探讨宣肺败毒方治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制。方法:借助中药系统药理学分析平台(TCMSP)检索宣肺败毒方有效活性成分及作用靶标,运用GeneCards等数据库获取COVID-19的相关靶标基因并与宣肺败毒方的作用靶标取交集获取治疗靶标。将治疗靶标上传STRING数据库获取蛋白交互作用(PPI)信息,利用Cytoscape构建药物-靶点-疾病网络、靶点蛋白高置信度PPI网络、活性成分-靶点-通路网络。利用Bioconductor中的R包对潜在作用靶点进行GO功能分析和KEGG通路富集分析。将主要活性成分分别与SARS-CoV-2的3CL水解酶(3CLPro)和血管紧张素转换酶2(ACE2)及关键靶标进行分子对接。结果:筛选出宣肺败毒方有效活性成分共99个,其中作用于COVID-19的22个活性成分可通过52个潜在靶标作用于COVID-19。富集得到GO中1364个生物过程条目和22条KEGG通路,涉及IL-17、JAK-STAT、MAPK、NF-κB、PI3K-Akt、Th1和Th2细胞分化、Th17细胞分化、T细胞受体、血管内皮生长因子(VEGF)和沙门氏菌感染等路径。分子对接结果显示宣肺败毒方中的木犀草素、β-谷甾醇、芒柄花黄素、紫檀素等活性成分与3CLPro和ACE2有较好的结合性,并且与核心靶点也有较好的结合性。结论:宣肺败毒方主要通过黄酮类和植物淄醇类活性成分与SARS-CoV-2的ACE2和3CLPro受体结合,抑制病毒入侵及病毒复制,在病毒感染细胞后可能通过调节IL-6、MAPK3、MAPK1、IL-1β、CCL2、EGFR、NOS2等关键靶点发挥抗炎、抗细胞因子风暴、抗氧化、调节机体免疫的作用来治疗COVID-19。

基于疾病传变谈新型冠状病毒肺炎与抗疫三方

基于疾病传变理论,对新型冠状病毒肺炎的病因、病机、传变规律与抗疫三方的临床应用规律进行总结。归纳得出新型冠状病毒肺炎病因以寒湿疫毒为主,兼有伏燥、火热等,疾病初起病机为虚在太阴,太阳气化失司,少阳枢机不利,以致气不摄津,水湿内生,入里化热伤阴。抗疫三方可分经、分脏腑、分三焦施治,使上中下三焦气机正常运转,以达利水祛湿、行水布津、润燥除热之功。清肺排毒汤主寒湿之象显著,以射干麻黄汤温化水饮;宣肺败毒方主稍有化热之象,以葶苈子泻肺逐水;化湿败毒方主热象显现,以葶苈子泻肺逐水、生大黄清热解毒。三方药物及药性各有侧重,然均立足于分治三焦气机以祛湿,需辨证论治。

“肺主通调水道”对治疗新型冠状病毒感染“三方”的理论指导

“肺主通调水道”是肺的主要生理功能之一,也是中医学辨证论治的重要理论基础,对临床处方也有很大的指导意义。文章通过归纳中医专家对新型冠状病毒感染的病机认识,对“肺主通调水道”的条文认识,分析治疗新型冠状病毒感染有效的清肺排毒汤、宣肺败毒方和化湿败毒方三方的药物组成和方解,进而为理解“肺主通调水道”提供新的思考视角,以加深中医理论内涵研究并能对临床进行理论指导。

中药早期干预对新型冠状病毒肺炎重症患者疾病转归影响的回顾性临床研究

目的回顾性分析新型冠状病毒肺炎(简称新冠肺炎)重症患者的临床资料,探讨中药早期干预对新冠肺炎重症患者疾病转归的影响。方法纳入武汉市中医医院2020年1月25日—3月10日收治的重症(重型、危重型)新冠肺炎患者72例,根据最早应用中药干预时间分为早期干预组(发病3天内服药)55例,非早期干预组(发病4天及以上服药)17例。两组患者均辨证给予宣清和化方、感冒退热方、新冠2号方(宣肺败毒方)汤剂及连花清瘟胶囊、喜炎平注射剂、血必净注射剂。分别统计两组患者入院时及入院7天后的实验室指标、急性生理学及慢性健康状况评分系统Ⅱ(ApacheⅡ)评分、序贯性脏器功能衰竭评分(SOFA评分)、肺部CT情况,统计两组患者住院时间并比较临床结局的差异。结果两组入院时一般情况及实验室检测指标比较差异无统计学意义(P>0.05)。入院7天后两组患者外周血白细胞(WBC)、中性粒细胞(N)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、丙氨酸氨基转移酶(AST)、门冬氨酸氨基转移酶(ALT)、D-二聚体(D-dimer)等实验室指标差异无统计学意义(P>0.05);早期干预组患者尿素氮(BUN)、C反应蛋白(CRP)、降钙素原(PCT)、ApacheⅡ评分、SOFA评分较非早期干预组降低(P<0.05),淋巴细胞计数(L)较非早期干预组升高(P<0.05)。早期干预组住院时间中位数为20天,非早期干预组为22天,两组比较差异无统计学意义(P>0.05)。早期干预组患者的死亡率(18.2%,10/55)低于非早期干预组(52.9%,9/17,P<0.05),治愈出院率(78.2%,43/55)高于非早期干预组(47.1%,8/17,P<0.05)。结论中药早期干预能够减轻新冠肺炎重症患者的炎症反应,调节患者免疫功能,促进肺部炎症的吸收,降低死亡率。