Font Size: a A A

Research On COVID-19 Drug Target Discovery Methods Based On Metabolic Analysis

Posted on:2024-06-07Degree:MasterType:Thesis
Country:ChinaCandidate:Y L ZhaoFull Text:PDF
GTID:2544306929990339Subject:Computer software and theory
Abstract/Summary:PDF Full Text Request
The COVID-19 pandemic has severely affected social and public life in countries around the world.However,there is still a lack of effective treatment methods,and it is necessary to find treatment strategies from various aspects.Metabolic reprogramming is an important hallmark in the development of many diseases.Viruses do not have a complete cellular structure to independently synthesize what they need,they must rely on the metabolic system of the host cell to complete their own replication.Some researchers have started from metabolism,looking for the molecular mechanism of COVID-19 and corresponding treatment plan.However,most of the current researches focus on specific metabolic pathways and do not analyze metabolic characteristics at the level of metabolic system.Starting from the level of metabolic system,understanding the metabolic characteristics of host cells invaded by viruses at the level of metabolic system,discovering drug targets,and providing new ideas for the treatment of this disease.Based on the interaction between SARS-CoV-2 protein and human genes as well as the gene expression data of host cells infected with the virus,this dissertation proposes a method for COVID-19 drug target discovery based on metabolic analysis.By reconstructing the metabolic network model of host cells invaded by viruses,the metabolic characteristics of host cells were analyzed by flux balance analysis,gene knockout,genotoxicity testing and other methods,and drug targets were found.The main work includes:(1)Proposing a COVID-19 drug target discovery method based on the interaction relationship between SARS-CoV-2 proteins and human genes.The metabolic network model of host cells was reconstructed using host genes highly correlated with viral proteins,and potential drug targets were identified by gene knockout and genotoxicity tests.The drug targets PLPBP and CTH have been proved to be related to COVID-19,and MTR has also been proved to be involved in the pathogenesis of other diseases.These targets can provide theoretical guidance for the treatment of COVID19.(2)Proposing a method for COVID-19 drug target discovery based on host cell gene expression data.The host cell metabolic network model was reconstructed from the gene expression data of host cells in the infected lung.The drug target PLPBP was consistent with the predicted results based on protein interaction,which proved the reliability of this research.BCAT1 and BCAT2 have also been shown to be closely related to the pathogenesis of COVID-19,which is valuable for further research.(3)Proposing a method for COVID-19 drug target discovery in complex diseases.Methods based on the gene expression data of lung cancer cells infected with SARS-CoV-2 and those not infected with SARS-CoV-2,differential analysis was carried out,and differentially up-regulated genes were extracted after SARS-CoV-2 invaded lung cancer cells.Drug targets have also been proved by relevant literature to be involved in inflammatory responses in COVID-19,providing clues and support for specific treatment of COVID-19 in complex diseases.
Keywords/Search Tags:Metabolic Network, Metabolism, Metabolic System, Drug Target, COVID-19, Complex Disease
PDF Full Text Request
Related items