AUTHOR=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 

TITLE=Exploring the mechanism of action of Xuanfei Baidu granule (XFBD) in the treatment of COVID-19 based on molecular docking and molecular dynamics

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.965273

DOI=10.3389/fcimb.2022.965273

ISSN=2235-2988

ABSTRACT=Purpose: The Corona Virus Disease 2019 (COVID-19) pandemic has become a global challenge. The latest research has proved that Xuanfei Baidu granule (XFBD) may significantly improve patient's clinical symptoms, increase the number of white blood cells and lymphocytes to improve immunity, and also exert anti-inflammatory effect. 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. Methods: We screened out the key active ingredients in XFBD through the TCMSP database, and 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 established 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 binding free energy, the number of hydrogen bonds, the stability of the protein target at the residue level, the radius of gyration and the solvent accessible surface area. Results: XFBD had 1308 gene targets, COVID-19 had 4600 gene targets, the intersection gene targets were 548. GO and KEGG analysis revealed that XFBD played a vital role by the signaling pathways of inflammation and immune response. 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. Conclusion: 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.