Protease inhibitor DUBs-IN-1 suppresses proliferation of Marek's disease virus in chicken cells
Vaccination is a main measure for protecting chickens against Marek's disease,while it is not able to suppress the infection,proliferation,transmission,and virulence enhancement on Marek's disease virus.Inhibiting the proliferation of Marek's disease virus in chicken is therefore an im-portant option for enhancing defense effectiveness.In this study,a compound,DUBs-IN-1,was found to inhibit the activity of MDV049,a protease encoded by Marek's disease virus,via screening a protease inhibitor library using MDV049 as target and ubiquitin probe.Molecular docking re-vealed that DUBs-IN-1 can interact with the residues which formed the catalytic pocket of MDV049,blocking the interaction between Ub substrate and the catalytic center of MDV049,then suppress the activity of MDV049 with competitive inhibition.Using the CPE model,it was found that DUBs-IN-1 at the concentration of 0.35 and 0.70 µmol/L significantly inhibited the CPE in-duced by Marek's disease virus in CEF cells.Quantitative analysis revealed that DUBs-IN-1 inhibi-ted the proliferation of Marek's disease virus in CEF cells(P＜0.01).Furthermore,it was found that the administration of 80 and 150 pg/(kg·d)of DUBs-IN-1 in chicken infected by Marek's disease virus significantly inhibited the proliferation of MDV in T cells(P＜0.01).In summary,this study demonstrated that the compound DUBs-IN-1 is able to inhibit the proliferation of Marek's disease virus in chicken cells,laying a theoretical and practical foundation for further de-velopment of the drugs against Marek's disease virus.
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维普
