The protease inhibitor p-nitrophenyl-p' -guanidinobenzoate inactivates sindbis and other enveloped viruses.

Sindis virions were inactivated by the protease inhibitor p-nitrophenyl-p′-guanidinobenzoate (NPGB) in a pH-, temperature-, and time-dependent reaction that decreased the titer of infectious virus by 4 to 5 logs. Treated virions remained structurally intact and competent for adsorption and penetration into host cells but failed to induce viral-specific RNA synthesis. Viral RNA from NPGB-treated virions was defective both as a messenger RNA in an in vitro protein synthesizing system and as a source of infectious RNA when tested in BHK cells. Additional studies with NPGB-treated defective-interfering particles and complementation tests with temperature-sensitive mutants of Sindbis virus suggested that NPGB-inactivated RNA could not serve as a template for replication. NPGB inactivated a variety of other enveloped viruses including influenza, Rous sarcoma, and lactic dehydrogenase virus but had no effect on the nonenveloped encephalomyocarditis and reo viruses. Thus, NPGB appears to inactivate virions by penetrating the viral envelope and acylating sensitive sites on viral RNA.