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PMID: 10023767 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

An antiviral mechanism of nitric oxide: inhibition of a viral protease.

Immunity ·Vol. 10 ·No. 1 ·1999-01-00 ·Pages 21-8

Saura M, Zaragoza C, McMillan A, Quick RA, Hohenadl C, Lowenstein JM, Lowenstein CJ

Abstract

Although nitric oxide (NO) kills or inhibits the replication of a variety of intracellular pathogens, the antimicrobial mechanisms of NO are unknown. Here, we identify a viral protease as a target of NO. The life cycle of many viruses depends upon viral proteases that cleave viral polyproteins into individual polypeptides. NO inactivates the Coxsackievirus protease 3C, an enzyme necessary for the replication of Coxsackievirus. NO S-nitrosylates the cysteine residue in the active site of protease 3C, inhibiting protease activity and interrupting the viral life cycle. Substituting a serine residue for the active site cysteine renders protease 3C resistant to NO inhibition. Since cysteine proteases are critical for virulence or replication of many viruses, bacteria, and parasites, S-nitrosylation of pathogen cysteine proteases may be a general mechanism of antimicrobial host defenses.

MeSH Terms
3C Viral Proteases Amino Acid Substitution/genetics Antiviral Agents/pharmacology Binding Sites Cysteine/genetics,metabolism Cysteine Endopeptidases/genetics,metabolism Cysteine Proteinase Inhibitors/pharmacology,physiology Enterovirus B, Human/drug effects,enzymology HeLa Cells Humans Hydrolysis/drug effects Mutagenesis, Site-Directed Nitric Oxide/pharmacology,physiology Nitroso Compounds/metabolism Serine/genetics Viral Proteins/antagonists & inhibitors,metabolism
Chemicals
Antiviral Agents Cysteine Proteinase Inhibitors Nitroso Compounds Viral Proteins Nitric Oxide Serine Cysteine Endopeptidases 3C Viral Proteases 3C proteases Cysteine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Saura M
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Zaragoza C
McMillan A
Quick R A
Hohenadl C
Lowenstein J M
Lowenstein C J
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1074-7613
DOI
10.1016/s1074-7613(00)80003-5
Published
1999-01-00
Pages
21-8
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC7129050
Subset
IM
Grants
NHLBI NIH HHS · P50 HL52315 · United States
NHLBI NIH HHS · R01 HL53615 · United States
External Links
PubMed source DOI: 10.1016/s1074-7613(00)80003-5 PMC Full Text View journal details
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