Molecular Dynamics Simulation Of The Interaction Between The Novel Coronavirus Main Protease And Its Potential Inhibitors

New Coronavirus(SARS-CoV-2)was originally named New Coronavirus in2019 or n CoV in 2019.On March 11,2020,because of the rapid spread of the virus in this infection,who announced that sars-cov-2 infection was a global pandemic.As of June 2021,sars-cov-2 has infected more than 170 million people and caused more than 3.8 million deaths,which has posed a serious threat to global human health.New Coronavirus is a coronavirus family.?-Coronavirus is a enveloped positive single stranded RNA virus.It contains 14 open reading frames(ORFs),and the main reading frame ORF1 ab encodes two overlapping multi proteins(pp1a,pp1ab).The completion of its life cycle requires a variety of viral proteins and host cell proteins to cooperate in a certain order.Among them,3-chymotrypsin like protease(also known as main protease,Mpro)and papain like protease(Plpro)cut pp1 a and pp1 ab to form 16 non structural proteins(nsp1-16),which are necessary for the formation of replication transcription complex.And the main protease did not find similar structure in human body,so the main protease is an ideal target for the development of anti COVID-19 drugs.In this study,the main protease of SARS-CoV-2 and five natural compound molecules(cyclomorusin,dieckol,euscaphic acid,furosin and lappadilactone)were used as the research objectives.Firstly,the complex models of SARS-CoV-2 main protease and five natural compound molecules were constructed respectively by using the calculation and analysis methods of molecular docking and molecular dynamics simulation,And the complex model of SARS-CoV-2 main protease and reserpine as the reference target.Then,through long-time molecular dynamics simulation,the stable configurations of the above six complex systems were obtained.Through the comprehensive comparative analysis of the molecular dynamics simulation data of six complex systems,the results show that among the five candidate molecules,furosin and dieckol are significantly better than reserpine.Therefore,furosin and dieckol may be more promising as inhibitors of SARS-CoV-2major proteinase than reserpine.The results of this study can provide a theoretical basis for the design and modification of drug molecules targeting the main protease of COVID-19,and provide reference for subsequent experiments and clinical applications.