目的 通過(guò)網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接的方法，初步探討小柴胡湯在新型冠狀病毒肺炎（COVID-19）治療中緩解發(fā)熱及抗病毒的可能作用機(jī)制。方法 運(yùn)用網(wǎng)絡(luò)藥理學(xué)方法分析小柴胡湯治療發(fā)熱的潛在靶點(diǎn)及通路；從TCMSP、PharmMapper數(shù)據(jù)庫(kù)收集小柴胡湯的成分和作用靶點(diǎn)；OMIM和Genecards數(shù)據(jù)庫(kù)收集發(fā)熱相關(guān)靶點(diǎn)；String數(shù)據(jù)庫(kù)構(gòu)建蛋白相互作用網(wǎng)絡(luò)，分析核心靶點(diǎn)；DAVID數(shù)據(jù)庫(kù)和KOBAS 3.0進(jìn)行基于基因本體論（GO）的功能富集分析和基于京都基因與基因組百科全書(shū)（KEGG）的通路富集分析；Cytoscape 3.2.7構(gòu)建成分-靶點(diǎn)-通路網(wǎng)絡(luò)圖。運(yùn)用分子對(duì)接技術(shù)篩選與新型冠狀病毒（SARS-CoV-2）以及SARS-CoV-2感染靶細(xì)胞關(guān)鍵受體血管緊張素轉(zhuǎn)化酶II（ACE2）結(jié)合力較強(qiáng)的活性成分，預(yù)測(cè)可能的結(jié)合位點(diǎn)。結(jié)果 網(wǎng)絡(luò)藥理學(xué)分析表明，小柴胡湯共篩選出165種活性成分，預(yù)測(cè)到靶點(diǎn)168個(gè)，篩選出發(fā)熱相關(guān)靶點(diǎn)7 006個(gè)，取交集得到小柴胡湯與發(fā)熱相關(guān)的靶點(diǎn)141個(gè)。GO富集到基因功能292個(gè)，KEGG富集到基因通路30條。分子對(duì)接結(jié)果表明，小柴胡湯的主要活性成分與SARS-CoV-2和ACE2均有較強(qiáng)的結(jié)合能力，其中β-谷甾醇、豆甾醇和3'-羥基-4'-O-甲基葡萄糖苷為結(jié)合最強(qiáng)的3個(gè)有效成分。結(jié)論 網(wǎng)絡(luò)藥理學(xué)方法初步探討了小柴胡湯緩解COVID-19發(fā)熱的作用機(jī)制，β-谷甾醇、豆甾醇和3'-羥基-4'-O-甲基葡萄糖苷可能為小柴胡湯中主要發(fā)揮抑制SARS-CoV-2的成分，為進(jìn)一步的研究提供了方向。

Objective The aim of this article was to study the potential antivirus and fever reducing mechanisms of Xiaochaihu Decoction (XCHD) on novel coronavirus pneumonia based on network pharmacology and molecular docking method. Methods Firstly, the potential targets and pathways of XCHD on fever were analyzed using network pharmacology. Compounds and potential targets in XCHD were screened using TCMSP and PharmMapper databases. The targets in fever reducing were identified from OMMI and Genecards databases. The protein-protein interaction network was established by String database to analyze key targets. The gene oncology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) analysis of key targets were also conducted to generate the relative pathways based on DAVID and KOBAS 3.0 databases, respectively. The compound-target-pathway network was established using Cytoscape 3.2.7. In addition, we used molecular docking method to identify the crucial compounds with higher connectivity on SARS-CoV-2 and the angiotensin-converting enzyme 2 (ACE2). ACE2 has been identified as the key target of SARS-CoV-2 entering cells. The possible binding sites of compounds on SARS-CoV-2 and ACE2 were predicted. Results Network pharmacology analysis indicated that 165 active compounds and 168 relative targets were selected. A total of 7006 targets related to fever were identified. In addition, 141 potential targets of XCH on fever were identified. Totally, 292 GO terms of XCHD on fever and 30 pathways were identified using GO and KEGG analysis. Furthermore, molecular docking indicated that main active compounds in XCHD exhibited higher affinity with both SARS-CoV-2 and ACE2. Beta-sitosterol, stigmasterol, 3'-hydroxy-4'-O-methylglabridin were top three candidates with highest affinity. Conclusion In summary, our study identified the potential mechanisms of XCHD on fever. Besides, Beta-sitosterol, stigmasterol, 3'-hydroxy-4'-O-methylglabridin could be the key compounds to exert anti-viral effects against SARS-CoV-2. Our prediction also provided the research fields to further study the mechanisms of XCH on SARS-CoV-2 infection in future.

R285.5

天津中醫(yī)藥大學(xué)治未病校級(jí)項(xiàng)目（XJ201801）