Screening For Drug Fragments For HRV2 2A Proteinase

Human rhinovirus 2(HRV2),is a member of the Enterovirus genus in the Picornaviridae family.There are three HRV subtypes,HRV-A,HRV-B and HRV-C,and HRV2 belongs to HRV-A.HRV have long been known to be the main etiologic agent of "common colds",which can cause respiratory tract infections and can also lead to the exacerbation of chronic lung diseases.Efforts at vaccine development are hindered by the existence of more than 100 HRV serotypes with high-level sequence variability in the antigenic sites.There are currently no specific antiviral agents for the prevention and treatment of HRV infection.2A proteinase(2Apro)is a multi-functional cysteine proteinase encoded in the HRV2 genome.2Apro cleaves the viral precursor protein at the junction between VP12A.In addition,2Apro plays a critical role in shutting down the host protein synthesis and influencing the nucleo-cytoplasm by disrupting the structure of the nuclear pore complex(NPC).With its essential role in the viral replication,2Apro could be a high value drug target for antiviral intervention.In this these,a HRV2 2A mutant(C106A)was expressed and purified for structural characterization.By screening and optimizing the crystallization conditions of the protein,we obtained crystals and resolved the structure.The thermal shift assay,isothermal titration calorimetry and fluorescence spectroscopy were used to screen a fragment compound library.At the conclusion of this program,eight drug fragments that could bind HRV2 2A(C106A)were obtained.This work lays a foundation for developing drugs against HRV infection and further research on 2Apro.