Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections [version 2; peer review: 1 approved, 2 approved with reservations]
Although the antimicrobial potential of nitric oxide (NO) is widely published, it is little used clinically. NO is a key signalling molecule modulating vascular, neuronal, inflammatory and immune responses. Endogenous antimicrobial activity is largely mediated by high local NO concentrations produce...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2021-10-01
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| Series: | F1000Research |
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| Online Access: | https://f1000research.com/articles/10-536/v2 |
| _version_ | 1798040617239969792 |
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| author | Christopher M. Coleman Adam L. Gordon Wei Shen Lim Andrew J. Webb Philip M. Bath |
| author_facet | Christopher M. Coleman Adam L. Gordon Wei Shen Lim Andrew J. Webb Philip M. Bath |
| author_sort | Christopher M. Coleman |
| collection | DOAJ |
| description | Although the antimicrobial potential of nitric oxide (NO) is widely published, it is little used clinically. NO is a key signalling molecule modulating vascular, neuronal, inflammatory and immune responses. Endogenous antimicrobial activity is largely mediated by high local NO concentrations produced by cellular inducible nitric oxide synthase, and by derivative reactive nitrogen oxide species including peroxynitrite and S-nitrosothiols. NO may be taken as dietary substrate (inorganic nitrate, L-arginine), and therapeutically as gaseous NO, and transdermal, sublingual, oral, intranasal and intravenous nitrite or nitrate. Numerous preclinical studies have demonstrated that NO has generic static and cidal activities against viruses (including β-coronaviruses such as SARS-CoV-2), bacteria, protozoa and fungi/yeasts in vitro. Therapeutic effects have been seen in animal models in vivo, and phase II trials have demonstrated that NO donors can reduce microbial infection. Nevertheless, excess NO, as occurs in septic shock, is associated with increased morbidity and mortality. In view of the dose-dependent positive and negative effects of NO, safety and efficacy trials of NO and its donors are needed for assessing their role in the prevention and treatment of infections. Trials should test dietary inorganic nitrate for pre- or post-exposure prophylaxis and gaseous NO or oral, topical or intravenous nitrite and nitrate for treatment of mild-to-severe infections, including due to SARS-CoV-2 (COVID-19). This review summarises the evidence base from in vitro, in vivo and early phase clinical studies of NO activity in viral, bacterial, protozoal and fungal infections. |
| first_indexed | 2024-04-11T22:10:10Z |
| format | Article |
| id | doaj.art-95d86aeac81d410686d5cf5c66d126e6 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-04-11T22:10:10Z |
| publishDate | 2021-10-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-95d86aeac81d410686d5cf5c66d126e62022-12-22T04:00:35ZengF1000 Research LtdF1000Research2046-14022021-10-011078470Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections [version 2; peer review: 1 approved, 2 approved with reservations]Christopher M. Coleman0Adam L. Gordon1Wei Shen Lim2Andrew J. Webb3Philip M. Bath4https://orcid.org/0000-0003-2734-5132Division of Infection, Immunity and Microbes, School of Life Sciences, University of Nottingham, Nottingham, Notts, NG7 2UH, UKUnit of Injury, Inflammation and Recovery Sciences, University of Nottingham, Derby, Derbyshire, DE22 3NE, UKRespiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, NG5 1PB, UKClinical Pharmacology, School of Cardiovascular Medicine & Sciences, Kings College London British Heart Foundation Centre of Research Excellence, St Thomas' Hospital, London, SE1 7EH, UKStroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, Notts, NG7 2UH, UKAlthough the antimicrobial potential of nitric oxide (NO) is widely published, it is little used clinically. NO is a key signalling molecule modulating vascular, neuronal, inflammatory and immune responses. Endogenous antimicrobial activity is largely mediated by high local NO concentrations produced by cellular inducible nitric oxide synthase, and by derivative reactive nitrogen oxide species including peroxynitrite and S-nitrosothiols. NO may be taken as dietary substrate (inorganic nitrate, L-arginine), and therapeutically as gaseous NO, and transdermal, sublingual, oral, intranasal and intravenous nitrite or nitrate. Numerous preclinical studies have demonstrated that NO has generic static and cidal activities against viruses (including β-coronaviruses such as SARS-CoV-2), bacteria, protozoa and fungi/yeasts in vitro. Therapeutic effects have been seen in animal models in vivo, and phase II trials have demonstrated that NO donors can reduce microbial infection. Nevertheless, excess NO, as occurs in septic shock, is associated with increased morbidity and mortality. In view of the dose-dependent positive and negative effects of NO, safety and efficacy trials of NO and its donors are needed for assessing their role in the prevention and treatment of infections. Trials should test dietary inorganic nitrate for pre- or post-exposure prophylaxis and gaseous NO or oral, topical or intravenous nitrite and nitrate for treatment of mild-to-severe infections, including due to SARS-CoV-2 (COVID-19). This review summarises the evidence base from in vitro, in vivo and early phase clinical studies of NO activity in viral, bacterial, protozoal and fungal infections.https://f1000research.com/articles/10-536/v2Bacteria COVID-19 fungus nitric oxide nitrate nitriteeng |
| spellingShingle | Christopher M. Coleman Adam L. Gordon Wei Shen Lim Andrew J. Webb Philip M. Bath Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections [version 2; peer review: 1 approved, 2 approved with reservations] F1000Research Bacteria COVID-19 fungus nitric oxide nitrate nitrite eng |
| title | Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections [version 2; peer review: 1 approved, 2 approved with reservations] |
| title_full | Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections [version 2; peer review: 1 approved, 2 approved with reservations] |
| title_fullStr | Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections [version 2; peer review: 1 approved, 2 approved with reservations] |
| title_full_unstemmed | Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections [version 2; peer review: 1 approved, 2 approved with reservations] |
| title_short | Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections [version 2; peer review: 1 approved, 2 approved with reservations] |
| title_sort | nitric oxide for the prevention and treatment of viral bacterial protozoal and fungal infections version 2 peer review 1 approved 2 approved with reservations |
| topic | Bacteria COVID-19 fungus nitric oxide nitrate nitrite eng |
| url | https://f1000research.com/articles/10-536/v2 |
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