Nitric oxide donors inhibit the coxsackievirus B3 proteinases 2A and 3C in vitro, virus production in cells, and signs of myocarditis in virus-infected mice.
The antiviral effect of nitric oxide (NO)-releasing compounds was investigated. Using bacterially expressed and purified proteinases 2A and 3C of coxsackievirus B3, in vitro assays demonstrated the inhibition of the 2A proteinase activity in the presence of S-nitroso- N-acetyl-penicillamine (SNAP), 3-morpholinosydnonimine (SIN-1), 4-phenyl-3-furoxancarbonitrile (PFC), glyceryl trinitrate (GTN), and isosorbide dinitrate (ISDN). Sodium nitroprusside (SNP), which releases NO after metabolization, had no effect. The 3C proteinase was inactivated by SNAP, GTN, and ISDN. The vasodilators GTN and ISDN, widely used in the treatment of angina pectoris, exhibited antiviral activity in CVB3-infected GMK cells. CVB3-infected NMRI outbred mice showed significantly reduced signs of myocarditis after treatment with GTN or ISDN. Inhibitors of the cellular inducible NO synthase (iNOS) such as N(G)-nitro-L-arginine methyl ester (L-NAME), N(G)-nitro-L-arginine (L-NNA), and S-methyl-isothiourea (SMT), had no deleterious effect on CVB3-infected NMRI mice, indicating that endogenous NO synthesis is unlikely to be a major defense mechanism after enterovirus infection of outbred mice.
D000086042:3C Viral Proteases; D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000187:drug effects*; D029822:Enterovirus B, Human / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D004769:Enterovirus Infections / Q000188:drug therapy / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D009205:Myocarditis / Q000188:drug therapy* / Q000821:virology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology* / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D005996:Nitroglycerin / Q000494:pharmacology / Q000627:therapeutic use; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014764:Viral Proteins / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D014764:Viral Proteins; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; C057400:picornain 2A, Picornavirus; D005996:Nitroglycerin; D010396:Penicillamine; D007548:Isosorbide Dinitrate; D019331:NG-Nitroarginine Methyl Ester