ApIV 3C蛋白酶抑制剂的虚拟筛选及活性测定

Antheraea pernyi iflavirus (ApIV) is an important cause of antheraea pernyi vomiting disease (AVD) which is seriously harming the production of Antheraea pernyi (A. pernyi) industry in China. ApIV is a single-stranded, positive-sense RNA virus, belong to the picornavirida family. Due to the significant role of 3C protease in virus replication, it is considered to be an attractive drug target for developing antiviral therapeutic agents. Although great efforts have been made to develop 3C protease inhibitors, no effective anti-viral therapy for the prevention or treatment of diseases caused by ApIV infection is available. In this study, an effective inhibitor of ApIV 3C protease, 3', 4', 5, 7-tetrahydroxyisoflavone (Orobol), was identified through virtual screening using molecular docking against natural product library. And the binding mode of Orobol with ApIV 3C protease was stable through molecular docking and molecular dynamics simulation (MD). The biological data displayed that the inhibition ratio of virus replication was stronger with the increase of the concentration of Orobol. And when the concentration of Orobol was 10μg/mL, the inhibition ratio reached 80.5%. In vivo assay also demonstrated that Orobol could inhibit viral replication in spodoptera frugiperda cell (Sf9) cells. Those results proved that Orobol was a novel inhibitor for the disease of antheraea pernyi caused by ApIV infections.