Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious fatal disease of swine. Few effective antiviral drugs are currently available against CSFV infections. To explore the feasibility of using capsid-targeted viral inactivation (CTVI) as an antiviral strategy against CSFV infections, we expressed the CSFV capsid protein (Cap) fused with the nuclease of Staphylococcus aureus (SN) in Escherichia coli and investigated its effects on the replication of CSFV in PK-15 cells. The results indicated that the fusion protein Cap-SN showed a strong Ca(2+)-dependent nuclease activity and inhibited the replication of CSFV in a dose-dependent manner, with complete inhibition at a concentration of 15 microg/ml, whereas the Cap fused with an enzymatically inactive SN (Cap-SN*) showed no nuclease activity or antiviral effects. Thus, the CTVI approach might be applicable to CSFV inhibition as a novel antiviral strategy.
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