An Antiviral Mechanism of Nitric Oxide
Open accessAbstract
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.
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•NO causes nitrosation of cysteine residues of essential proteins for viral replication.
“•NO causes nitrosation of the cysteine residues of essential proteins for viral replication [135].”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [135]
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References 71 · Cited by 245
Research works printed but not linked: 1
- [19]Gorbalenya A.E Svitkin Y.V Protease of encephalomyocarditis virus: purification and role of SH groups in processing of the structural proteins precursor Biochemistry (USSR) 48 1983 385 395
- Authors
- Saura, M., Zaragoza, C., McMillan, A., Quick, R. A., Hohenadl, C., Lowenstein, J. M., & Lowenstein, C. J.
- Affiliations
- Johns Hopkins University (US)
- Helmholtz Munich (DE)
- Brandeis University (US)
- Corresponding author
- Lowenstein, Charles J
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 10
- Issue
- 1
- Pages
- 21-28
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC7129050
- OpenAlex
- W2087540023
- Cited by
- 245
- References
- 71
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 11 · 2023: 10 · 2022: 13 · 2021: 20 · 2020: 23 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 5 · 2013: 4 · 2012: 3
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Immunity (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl053615-04)
- National Heart, Lung, and Blood Institute (P50HL52315, P50HL052315, R01-HL53615)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- nitric oxide, antiviral immunity, S-nitrosylation, Coxsackie virus, cysteine protease, protease inhibition, viral polyprotein processing, host defense against viruses, active site cysteine
- MeSH terms
- 3C Viral Proteases, Antiviral Agents, Binding Sites, Cysteine, Cysteine Endopeptidases, HeLa Cells, Humans, Hydrolysis, Nitric Oxide, Nitroso Compounds, Serine, Viral Proteins, Cysteine Proteinase Inhibitors, Mutagenesis, Site-Directed, Amino Acid Substitution, Enterovirus B, Human
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