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Nitric Oxide in the Treatment of COVID‐19: Nasal Sprays, Inhalants and Nanoparticles

Wright et al., Biochemistry Research International, doi:10.1155/bri/8846903, Oct 2025
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Review of nitric oxide (NO) as a therapeutic for COVID-19, focusing on its administration as a nasal spray, inhalant, or via nanoparticles. Clinical trials on nitric oxide nasal spray (NONS) have shown it to be an effective and safe therapy that significantly reduces SARS-CoV-2 viral load. Authors note that inhaled nitric oxide (iNO) has also been shown to improve oxygenation and respiratory outcomes in COVID-19 patients with varying severity, but with inconsistent survival benefits for severe patients. While iNO carries risks like methaemoglobin and nitrogen dioxide formation, authors found studies showing these levels remained within safe limits. The rationale for NO treatment is based on findings that COVID-19 patients often have decreased NO bioavailability, and NO is believed to inhibit the virus by S-nitrosylation of the host's ACE2 receptor or viral proteases.
Reviews covering nitric oxide for COVID-19 include1-6.
Wright et al., 13 Oct 2025, peer-reviewed, 3 authors. Contact: sophia.bryan04@uwimona.edu.jm.
Abstract: Wiley Biochemistry Research International Volume 2025, Article ID 8846903, 13 pages https://doi.org/10.1155/bri/8846903 Review Article Nitric Oxide in the Treatment of COVID-19: Nasal Sprays, Inhalants and Nanoparticles Amarley Wright ,1 Donovan McGrowder ,2 and Sophia Bryan 1 1 Department of Basic Medical Sciences, Biochemistry Section, Faculty of Medical Sciences, Te University of the West Indies, Mona, Kingston 7, Jamaica 2 Department of Pathology, Faculty of Medical Sciences, Te University of the West Indies, Mona, Kingston 7, Jamaica Correspondence should be addressed to Sophia Bryan; sophia.bryan04@uwimona.edu.jm Received 28 May 2023; Revised 7 June 2023; Accepted 11 August 2025 Academic Editor: Harleen Khatra Copyright © 2025 Amarley Wright et al. Biochemistry Research International published by John Wiley & Sons Ltd. Tis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Although the World Health Organization has declared that the coronavirus disease (COVID-19) is not a public health emergency of international concern anymore, it has negatively impacted the world, and efective treatment for this pandemic remains a major priority. Vaccine efectiveness has been a matter of concern given the evolution of variants and subvariants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Tus, continued protection against SARS-CoV-2 and its variants is still necessary and could work alone or in parallel with vaccinations to treat COVID-19 in the future. Further, fndings from in vitro and in vivo studies have noted the efectiveness of high dosages of nitric oxide (NO) as an antimicrobial agent against respiratory pathogens such as bacteria, viruses and fungi. NO has been previously utilized in the management of SARS-CoV and has shown a similar antiviral efect with SARS-CoV-2 in vivo and in vitro. Efective therapy with NO can be used to target several stages of COVID-19 infection to prevent transmission and progression of the disease. Te unique properties of NO allow this simple, gaseous molecule to be administered in various forms. NO can be used as an inhalant, in the form of NO donor drugs such as Snitrosothiols and more recently as NO-releasing nanoparticles (NO-nps). Tis review summarizes the bioavailability of NO in COVID-19 patients and highlights in vivo and in vitro studies as well as clinical trials with NO administered as a nasal spray, inhalant, or via nanodelivery for therapeutic applications for COVID-19 and other respiratory infections in the future. Keywords: antimicrobial efect; COVID-19; inhaled nitric oxide; nanoparticles; nitric oxide
DOI record: { "DOI": "10.1155/bri/8846903", "ISSN": [ "2090-2247", "2090-2255" ], "URL": "http://dx.doi.org/10.1155/bri/8846903", "abstract": "<jats:p>Although the World Health Organization has declared that the coronavirus disease (COVID‐19) is not a public health emergency of international concern anymore, it has negatively impacted the world, and effective treatment for this pandemic remains a major priority. Vaccine effectiveness has been a matter of concern given the evolution of variants and subvariants of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Thus, continued protection against SARS‐CoV‐2 and its variants is still necessary and could work alone or in parallel with vaccinations to treat COVID‐19 in the future. Further, findings from in vitro and in vivo studies have noted the effectiveness of high dosages of nitric oxide (NO) as an antimicrobial agent against respiratory pathogens such as bacteria, viruses and fungi. NO has been previously utilized in the management of SARS‐CoV and has shown a similar antiviral effect with SARS‐CoV‐2 in vivo and in vitro. Effective therapy with NO can be used to target several stages of COVID‐19 infection to prevent transmission and progression of the disease. The unique properties of NO allow this simple, gaseous molecule to be administered in various forms. NO can be used as an inhalant, in the form of NO donor drugs such as S‐nitrosothiols and more recently as NO‐releasing nanoparticles (NO‐nps). This review summarizes the bioavailability of NO in COVID‐19 patients and highlights in vivo and in vitro studies as well as clinical trials with NO administered as a nasal spray, inhalant, or via nanodelivery for therapeutic applications for COVID‐19 and other respiratory infections in the future.</jats:p>", "alternative-id": [ "10.1155/bri/8846903" ], "article-number": "8846903", "assertion": [ { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Received", "name": "received", "order": 0, "value": "2023-05-28" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "2025-08-11" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Published", "name": "published", "order": 3, "value": "2025-10-13" } ], "author": [ { "ORCID": "https://orcid.org/0000-0002-6392-4783", "affiliation": [], "authenticated-orcid": false, "family": "Wright", "given": "Amarley", "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0001-8018-7722", "affiliation": [], "authenticated-orcid": false, "family": "McGrowder", "given": "Donovan", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-4266-7781", "affiliation": [], "authenticated-orcid": false, "family": "Bryan", "given": "Sophia", "sequence": "additional" } ], "container-title": "Biochemistry Research International", "container-title-short": "Biochemistry Research International", "content-domain": { "crossmark-restriction": true, "domain": [ "onlinelibrary.wiley.com" ] }, "created": { "date-parts": [ [ 2025, 10, 13 ] ], "date-time": "2025-10-13T12:34:19Z", "timestamp": 1760358859000 }, "deposited": { "date-parts": [ [ 2025, 10, 13 ] ], "date-time": "2025-10-13T12:34:32Z", "timestamp": 1760358872000 }, "editor": [ { "affiliation": [], "family": "Khatra", "given": "Harleen", "sequence": "additional" } ], "indexed": { "date-parts": [ [ 2025, 10, 13 ] ], "date-time": "2025-10-13T13:12:34Z", "timestamp": 1760361154213, "version": "build-2065373602" }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2025, 1 ] ] }, "journal-issue": { "issue": "1", "published-print": { "date-parts": [ [ 2025, 1 ] ] } }, "language": "en", "license": [ { "URL": "http://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 285, "start": { "date-parts": [ [ 2025, 10, 13 ] ], "date-time": "2025-10-13T00:00:00Z", "timestamp": 1760313600000 } } ], "link": [ { "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1155/bri/8846903", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "311", "original-title": [], "prefix": "10.1155", "published": { "date-parts": [ [ 2025, 1 ] ] }, "published-online": { "date-parts": [ [ 2025, 10, 13 ] ] }, "published-print": { "date-parts": [ [ 2025, 1 ] ] }, "publisher": "Wiley", "reference": [ { "article-title": "Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19)", "author": "Gomes C.", "journal-title": "Brazilian Journal of Implantology and Health Sciences", "key": "e_1_2_13_1_2", "volume": "2", "year": "2020" }, { "DOI": "10.1126/science.abm8108", "doi-asserted-by": "publisher", "key": "e_1_2_13_2_2" }, { "article-title": "SARS-CoV-2, SARS-CoV, and MERS-COV: A Comparative Overview", "author": "Rabaan A. 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