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

Abstract

PurposeThe 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.MethodsWe 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.ResultsXFBD 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.ConclusionFor 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.

Comparative transcriptomic analyzes of human lung epithelial cells infected with wild-type SARS-CoV-2 and its variant with a 12-bp missing in the E gene

“…IL-6 might be a reliable indicator for the COVID-19 severity, and a higher level of IL-6 concentration was found in severe COVID-19 patients than in the moderate or mild groups ( Bergantini et al, 2022 ). The CSF2 protein was inhibited to reduce the production of inflammatory factors and chemotaxis of inflammatory cells ( Xiong et al, 2022 ). CXCL10, also known as interferon gamma-induced protein 10 (IP-10), is a pro-inflammatory chemokine ( Coperchini et al, 2020 ).…”

Five traditional Chinese medicine formulations for addressing COVID-19

“…Baicalein has shown a stable appeal for SARS-CoV-2, while Quercetin has demonstrated a strong affinity for ACE2 and 3CL. The quercetin exerts its inhibitory effect on COVID-19 by competitively binding to the S-protein, thereby preventing its interaction with ACE2 [15] Furthermore, quercetin possesses the capacity to regulate the activation of MAPK, a routine responsible for the production of inflammatory factors, thus aiding in the enhancement of the immune system and viral defense [6]. Moreover, quercetin can hinder the PI3K-Akt pathway by reducing the presence of AKT1.…”