Inhibitor Screening And Structural Study Of 2C Protein From Enterovirus 71

Hand,foot and mouth disease(HFMD)is an important infectious disease.It affects millions in China each year.Most of the victims are under the age of five.Symptoms of HFMD include herpes on the skin around the hands,feet,mouth and anus,as well as fever.HFMD is highly contagious,and even adults can be asymptomatic carriers.Enterovirus 71(EV71)is one of the pathogens that causesHFMD,it is a particularly virulent infectious agent for HFMD as compared to other viruses.Its infection has a higher chance of leading to severe HFMD with additional symptoms such as neuropathic pulmonary edema,among others,and even death.There is currently no specific drug to counter EV71-related HFMD.The 2C helicase plays important roles in the viral life cycle of EV71,including immune escape,viral uncoating,RNA replication,and others.From the experience of developing antivirals against hepatitis C,targeting helicase is an effective strategy.It is quite possible that compounds to 2C protein will produce good drug candidates.In this study,the soluble fragment of 2C protein was expressed and purified for crystallization and establishing a system for structure-based drug design.The purified protein and the structural information offered the opposability of drug screening by thermal shift experiment and virtual screening.Among the several small molecules identified by thermal shift,compound P1217 0215 G04 showed strong effect in the thermal shift experiments.The docking experiment indicated that the compound could bind to 2C protein at a site at the interface of the oligomeric proteins.As the integrity of the hexameric 2C protein is essential for its activity,it is possible that this compound could interfere with the formation of active 2C to interrupt the viral life cycle.