Xiong Li, Cao Junfeng, Yang Xingyu, Chen Shengyan, Wu Mei, Wang Chaochao, Xu Hengxiang, Chen Yijun, Zhang Ruijiao, Hu Xiaosong, Chen Tian, Tang Jing, Deng Qin, Li Dong, Yang Zheng, Xiao Guibao, Zhang Xiao
Clinical Medicine, Chengdu Medical College, Chengdu, China.
Chengdu Medical College of Basic Medical Sciences, Chengdu, China.
Front Cell Infect Microbiol. 2022 Aug 10;12:965273. doi: 10.3389/fcimb.2022.965273. eCollection 2022.
The Corona Virus Disease 2019 (COVID-19) pandemic has become a challenge of world. The latest research has proved that (XFBD) significantly improved patient's clinical symptoms, the compound drug improves immunity by increasing the number of white blood cells and lymphocytes, and exerts anti-inflammatory effects. However, the analysis of the effective monomer components of XFBD and its mechanism of action in the treatment of COVID-19 is currently lacking. Therefore, this study used computer simulation to study the effective monomer components of XFBD and its therapeutic mechanism.
We screened out the key active ingredients in XFBD through TCMSP database. Besides GeneCards database was used to search disease gene targets and screen intersection gene targets. The intersection gene targets were analyzed by GO and KEGG. The disease-core gene target-drug network was analyzed and molecular docking was used for verification. Molecular dynamics simulation verification was carried out to combine the active ingredient and the target with a stable combination. The supercomputer platform was used to measure and analyze the number of hydrogen bonds, the binding free energy, the stability of protein target at the residue level, the solvent accessible surface area, and the radius of gyration.
XFBD had 1308 gene targets, COVID-19 had 4600 gene targets, the intersection gene targets were 548. GO and KEGG analysis showed that XFBD played a vital role by the signaling pathways of immune response and inflammation. Molecular docking showed that I-SPD, Pachypodol and Vestitol in XFBD played a role in treating COVID-19 by acting on NLRP3, CSF2, and relieve the clinical symptoms of SARS-CoV-2 infection. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets, CSF2/I-SPD combination has the strongest binding energy.
For the first time, it was found that the important active chemical components in XFBD, such as I-SPD, Pachypodol and Vestitol, reduce inflammatory response and apoptosis by inhibiting the activation of NLRP3, and reduce the production of inflammatory factors and chemotaxis of inflammatory cells by inhibiting the activation of CSF2. Therefore, XFBD can effectively alleviate the clinical symptoms of COVID-19 through NLRP3 and CSF2.
2019年冠状病毒病（COVID-19）大流行已成为全球性挑战。最新研究证明，新冠病毒肺炎方（XFBD）能显著改善患者临床症状，该复方药物通过增加白细胞和淋巴细胞数量提高免疫力，并发挥抗炎作用。然而，目前缺乏对XFBD有效单体成分及其治疗COVID-19作用机制的分析。因此，本研究采用计算机模拟方法研究XFBD的有效单体成分及其治疗机制。
通过中药系统药理学数据库与分析平台（TCMSP）筛选出XFBD中的关键活性成分。此外，利用基因卡片（GeneCards）数据库搜索疾病基因靶点并筛选交集基因靶点。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）对交集基因靶点进行分析。分析疾病核心基因靶点-药物网络，并采用分子对接进行验证。进行分子动力学模拟验证，以使活性成分与靶点稳定结合。利用超级计算机平台测量和分析氢键数量、结合自由能、蛋白质靶点在残基水平的稳定性、溶剂可及表面积和回转半径。
XFBD有1308个基因靶点，COVID-19有4600个基因靶点，交集基因靶点为548个。GO和KEGG分析表明，XFBD通过免疫应答和炎症信号通路发挥重要作用。分子对接显示，XFBD中的异泽兰黄素（I-SPD）、粗榧醇和紫铆醇通过作用于NLRP3、集落刺激因子2（CSF2）发挥治疗COVID-19的作用，并缓解严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的临床症状。利用分子动力学证明活性成分与蛋白质靶点的结合稳定性，CSF2/I-SPD组合具有最强的结合能。
首次发现XFBD中的重要活性化学成分，如I-SPD、粗榧醇和紫铆醇，通过抑制NLRP3的激活减轻炎症反应和细胞凋亡，并通过抑制CSF2的激活减少炎症因子的产生和炎症细胞的趋化作用。因此，XFBD可通过NLRP3和CSF2有效缓解COVID-19的临床症状。
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