杜帅琳,王玉,张玲,万海同

• 1:浙江中医药大学

摘要(Abstract)：

目的探寻散寒化湿宣肺方(SHXF)中抗新型冠状病毒(SARS-CoV-2)的活性化合物。方法借助TCMSP等数据库检索SHXF方中苍术、陈皮、厚朴、藿香、草果、生麻黄、羌活、生姜、槟榔所含化学成分与作用靶点。通过Cytoscape软件绘制化合物-靶点网络图和PPI网络图对化合物和靶点进行拓扑分析。采用DAVID6.7数据库对靶点进行GO功能和KEGG通路富集分析;利用AutoDock Vina对SHXF关键化合物与SARSCoV-2 3CL水解酶和Nsp15蛋白进行分子对接。结果经筛选获得SHXF共85个活性化合物与214个作用靶点,关键靶点涉及Akt1、IL-6、MAPK3、VEGFA、JUN等。GO富集分析得到功能条目599个(P <0.05),其中生物过程(BP)460个,细胞组成(CC)55个,分子功能(MF)84个。KEGG通路获得113条(P <0.05),主要涉及甲型流感(Influenza A)信号通路、TLR(Toll-like receptor)信号通路、PI3K-Akt信号通路、HIF-1信号通路等。分子对接结果显示SHXF中槲皮素、柚皮素、谷甾醇等核心化合物与瑞德西韦等推荐用药亲和力相似。结论 SHXF中的槲皮素、柚皮素、谷甾醇等核心化合物可与SARS-CoV-2 3CL水解酶和Nsp15蛋白结合,或为治疗新型冠状病毒肺炎的活性化合物。

关键词(KeyWords)： 新型冠状病毒;新型冠状病毒肺炎;网络药理学;分子对接

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金重点项目（81930111)

作者(Author): 杜帅琳,王玉,张玲,万海同

参考文献(References)：

• [1] Wu F,Zhao S,Yu B,et al. A new coronavirus associated with human respiratory disease in China[J]. Nature,2020,579,265-269.
• [2] Zhou P,Yang X,Wang X,et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin[J]. Nature,2020,579,270-273.
• [3] Huang CL,Wang Y,Li XW,et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan China[J].Lancet,2020,395:10223.
• [4]刘千勇，王晓良.新型冠状病毒（2019-nCoV）的靶向药物研究策略[J].药学学报，2020,55(2):181-188.
• [5]国家卫生健康委员会.关于印发新型冠状病毒肺炎诊疗方案（试行第七版）的通知[EB/OL].[2020-04-17]. http：//www.nhc.gov.cn/yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb1989.shtml.
• [6] Hopkins AL. Network pharmacology[J]. Nat Biotechnol,2007,25(10):1110-1111.
• [7]黄启和，周福军，徐旭，等.基于分子对接技术虚拟筛选延胡索抗心肌缺血物质基础研究[J].中草药，2019,50(10):2355-2361.
• [8] Ru J,Li P,Wang J,et al. TCMSP:a database of systems pharmacology for drug discovery from herbal medicines[J]. J Cheminform,2014,6:13.
• [9] Ahmed SS,Ramakrishnan V. Systems biological approach of molecular descriptors connectivity:Optimal descriptors for oral bioavailability prediction[J]. PLoS One,2012,7(7):e40654.
• [10] Ursu O,Rayan A,Goldblum A,et al. Understanding druglikeness[J]. Wires Comput Mol Sci,2011,1(5):760-781.
• [11] UniProt Consortium T. Uniprot:the universal protein knowledgebase[J]. Nucleic AcidsResearch,2017,45(D1):D158-
• [12] DBu1r6l9e.y SK,Berman HM,Kleywegt GJ,et al. Protein Data Bank(PDB):the single global macromolecular structure archive[J]. Methods Mol Biol,2017,1607:627-641.
• [13]徐森楠，庄莉，翟园园，等.基于网络药理学研究二至丸防治骨质疏松症的物质基础与作用机制[J].中国药学杂志，2018,53(22):1914-1920.
• [14]汪迎. HIF-1、VEGF在慢性阻塞性肺疾病中的表达及临床意义[D].南昌：南昌大学，2019.
• [15] Ank N,Iversen MB,Bartholdy C,et al. An important role for typeⅢinterferon(IFN-α/IL-28)in TLR-induced antiviral activity[J]. Journal of Immunology,2008,180(4):2474-2485.
• [16] Heil Florian,Hemmi Hiroaki,Hochrein Hubertus,et al. Species-specific recognition of single-stranded RNA via tolllike receptor 7 and 8[J]. Science,2004,303:5663.
• [17] Urata,Shuzo,Ngo,Nhi,de la Torre,Juan Carlos. The PI3K/Akt pathway contributes to arenavirus budding[J]. Journal of Virology,2012,86(8):4578-4585.
• [18] Kindrachuk Jason,Ork Britini,Hart Brit J,et al. Antiviral potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for middle east respiratory syndrome coronavirus infection as identified by temporal kinome analysis[J]. Antimicrobial Agents&Chemotherapy,2015,59(2):1088-1099.