基于AlphaFold2分析猪流感病毒H3N2核衣壳蛋白及其纳米抗体的三维结构和相互作用位点OA

Swine influenza virus is a pathogen that seriously endangers the swine industry.Moreover,swine influenza virus could also infect humans,posing a significant threat to global public health.The main targets of currently approved antiviral drugs to treat influenza virus are neuraminidase and matrix-2 protein.The currently approved antiviral drugs to treat influenza virus have limitations due to the variability of influenza viruses and the development of drug resistance.The nucleoprotein of influenza virus is highly conserved among different strains,making it an ideal drug target.Nanobody is the smallest antibody fragment with a complete antigen-binding function.As nanobody show several advantages,it has become a candidate for the development of new therapeutic drugs for the treatment of many diseases.The identification of the interaction sites between drugs and target proteins is essential for drug development.AlphaFold2 has a high accuracy in predicting the three-dimensional structures of proteins,making the identification of the interaction sites between drugs and target proteins easier.In this study,AlphaFold2 was used to predict the three-dimensional structures of monomers of nucleoprotein of swine influenza virus H3N2 and its six specific nanobodies.Then,AlphaFold2 was used to predict the three-dimensional structure of the complex between nucleoprotein of swine influenza virus H3N2 and its six specific nanobodies.The results showed that the confidence levels of the three-dimensional structures of monomers of nucleoprotein of swine influenza virus H3N2 and its six specific nanobodies were reliable or very high.Among the three-dimension-al structures of the complexes,the confidence levels of the three-dimensional structure of the complex between one nanobody and the nucleoprotein was high,and the rest were low.The interaction site between one nanobody and the nucleoprotein of swine influenza virus H3N2 was preliminarily determined.This study provides a reference for the development of therapeutic nanobody drugs against influenza viruses.