The Interaction Between Antiviral Drugs And Protein And Molecular Simulation

In recent years,diseases caused by viral infection are becoming more and more common and wide spread,which makes it difficult to control and endanger people's lives and health seriously.However,the development of antiviral drugs is slow nowdays,and our understanding of antiviral drugs is insufficient.In view of the the virus is prone to produce resistance to antiviral drugs,it is necessary to strengthen the research of antiviral drugs.In this paper,three antiviral drugs(Boceprevir,Favipiravir and Velpatasvir)are selected to be investigated.Human serum albumin is the main transport protein in human plasma,and Trypsin is the target protein analogue of Boceprevir.Therefore,it is very important to study the interaction between these three drugs with Human serum albumin.It is believed that the interaction between Boceprevir with Trypsin will be beneficial to the clinical,pharmacodynamic and drug design.At the same time,three-dimensional quantitative structure-activity relationship(3D-QSAR)is used to provide reference for the design and synthesis of series of anti-hepatitis C virus drugs analogue of Boceprevir.The research contents are divided into three parts:(1)The interaction mechanism of Favipiravir and Velpatasvir with Human serum albumin was studied by various spectroscopy and molecular docking techniques.The results revealed that they formed static quenching complexes with Human serum albumin;numbers of binding sites were 1.Velpatasvir binds in the IIB region of HSA by hydrogen bond and hydrophobic force.Favipiravir binds in siteI IIA of HSA by hydrogen bond and van der Waals force.(2)The interaction of Boceprevir with Human serum albumin and Trypsin were studied and compared by various spectroscopy and molecular docking techniques.The results showed that the reaction of Boceprevir with Human serum albumin and Trypsin both were static quenching;numbers of binding sites were 1,and Boceprevir binds in siteI IIA of HSA by hydrogen bond and van der Waals force.Moreover,Boceprevir binds more closely to its target protein analogue Trypsin than Human serum albumin.(3)A series of serine protease inhibitors with the same nuclear parent as Boceprevir were used to study the relationship between structural information of inhibitors with inhibitory activity by 3D-QSAR method.Through analysis,11 compounds with new structure were designed,which have higher inhibitory activity on serine protease.All our results can provide reference for the design of new anti-hepatitis C virus drugs.