Abstract
Purpose: The Corona Virus Disease 2019 (COVID-19) pandemic has become a challenge of world. The latest research has proved that Xuanfei Baidu granule (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.
Methods: 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.
Results: 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.
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.
Keywords: COVID-19; Xuanfei Baidu granule; bioinformatics analysis; molecular docking; molecular dynamics.
【저자키워드】 COVID-19, molecular docking, Xuanfei Baidu granule, molecular dynamics., Bioinformatics analysis, 【초록키워드】 Treatment, Apoptosis, Inflammation, Anti-inflammatory effects, immune response, pandemic, Lymphocytes, Clinical symptoms, Immunity, SARS-COV-2 infection, bioinformatics, docking, molecular dynamics, binding free energy, database, binding energy, Protein, stability, White blood cell, Corona, therapeutic, Research, Patient, targets, ingredient, signaling pathway, molecular, mechanism of action, disease, platform, mechanism, binding, NLRP3, Combination, Inflammatory response, Analysis, GeneCard, inflammatory cell, Activation, clinical symptom, residue, TCMSP database, Intersection, treating COVID-19, hydrogen bonds, component, KEGG, chemotaxis, solvent, monomer, protein targets, radius of gyration, CSF2, Inflammatory factor, effective, Baidu, gene target, IMPROVE, analyzed, was used, carried, significantly, screened, reduce, inhibiting, alleviate, acting, Pachypodol, 【제목키워드】 Treatment, molecular, mechanism of action, Baidu,