Nitric Oxide (NO): A New Weapon in Fight against COVID-19

Findings from recently concluded phase 2 clinical trials in Canada and the UK suggest nitric oxide (NO) could be very helpful in preventing and treating COVID-19.

Nitric oxide NO, (not to be confused with nitrous oxide N₂O used as anaesthetic in clinical settings) also known as an endothelium-derived relaxing factor (EDRF) is a known biological signalling molecule which is synthesised endogenously and play key role in relaxation of smooth muscles of the blood vessel leading to vasodilation and increased blood flow. It is commonly used as prodrug Glyceryl trinitrate GTN to relieve chest pain (angina). Sildenafil (Viagra) uses the same nitric acid pathway for vasodilation.  

Another less explored property of nitric oxide (NO) is its antimicrobial activity against range of microbes including bacteria responsible for respiratory diseases such as hospital acquired pneumonia. Nitric oxide was also found to have significant antiviral properties. NO inhalation was shown to improve the condition of patients affected by SARS.  

Since SARS-CoV2 is genetically related to SARS-CoV, it was thought that NO could be effective against SARS-CoV2 as well ^1,2. The adverse clinical condition seen in COVID-19 is because SARS-CoV2 causes nitric oxide (NO) dysfunction in cells and tissues leading to reduced endogenous NO level and bioavailability. Therefore, enhancing nitric oxide (NO) availability exogenously through suitable means such as inhalation, nasal spray, gargle, releasing solutions etc should help COVID-19 patients³.  

Currently, several clinical trials are underway to test the effectiveness of NO as therapeutic and preventive agent for managing COVID-19. Important studies are below- 

Inhalation: Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID-19 (NoCovid): This phase 2 trial is sponsored by Massachusetts General Hospital and is testing whether inhalation of nitric oxide (NO) prevents progression in patients with mild to moderate COVID-19 disease.  NO Prevention of COVID-19 for Healthcare Providers (NOpreventCOVID) is another study by Massachusetts General Hospital and is designed to test whether nitric oxide gas inhalation prevents COVID-19 among healthcare workers.  

Nasal Spray: Nitric Oxide Nasal Spray for COVID-19 treatment: Sponsored by Ashford and St Peter’s Hospitals NHS Foundation Trust, this study aims to test whether nitric oxide (NO) delivered through a nasal spray treats mild COVID-19 symptoms.  

Releasing solutions: Nitric Oxide Releasing Solutions to Prevent and Treat Mild/Moderate COVID-19 Infection (NOCOVID) sponsored by SaNOtize, this phase2 clinical trial was conducted in Canada and is completed. The study tested effectiveness of its proprietary NORS (Nitric Oxide Releasing Solution) formulation in preventing and treating mild/moderate infections^4,5.  

As per press release by SaNOtize, the releasing solution NORS reduced the viral load by more than 95% in infected participants within 24 hours of treatment, and by more than 99% in 72 hours. The treatment accelerated clearance of SARS-CoV-2 by a factor of 16-fold versus a placebo which is very encouraging indeed. The company is planning Submission for Emergency Use Authorisation in the UK and Canada immediately⁶.  

Hope repurposing of Nitric Oxide (NO) proves helpful in preventing and treating COVID-19 cases soon.  

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References: 

1. Gianni S., Fakhr BS., et al 2020. Nitric oxide gas inhalation to prevent COVID-2019 in healthcare providers. Preprint. MedRxiv. Posted April 11, 2020. DOI: https://doi.org/10.1101/2020.04.05.20054544 

2. Pieretti JC., Rubilar O., et al 2021. Nitric oxide (NO) and nanoparticles – Potential small tools for the war against COVID-19 and other human coronavirus infections. Virus Research. Volume 291, 2 January 2021, 198202. DOI: https://doi.org/10.1016/j.virusres.2020.198202 

3. Fang W., Jiang J., et al 2021. The role of NO in COVID-19 and potential therapeutic strategies. Free Radical Biology and Medicine. Volume 163, Pages 153-162. Published 1 February 2021. DOI:https://doi.org/10.1016/j.freeradbiomed.2020.12.008 

4. US NLM 2021. Nitric Oxide Releasing Solutions to Prevent and Treat Mild/Moderate COVID-19 Infection (NOCOVID). ClinicalTrials.gov Identifier: NCT04337918. Available online at https://www.clinicaltrials.gov/ct2/show/NCT04337918?term=SaNOtize+nasal+spray&cond=Covid19&draw=2&rank=2 Accessed on 08 April 2021.  

5. SaNOtize, 2021. NORSTM – our platform technology. Available online at https://sanotize.com Accessed on 08 April 2021.  

6. SaNOtize, 2021. Press release – UK Clinical Trial Confirms SaNOtize’s Breakthrough Treatment for COVID19. Available online at https://www.businesswire.com/news/home/20210315005197/en/UK-Clinical-Trial-Confirms-SaNOtize’s-Breakthrough-Treatment-for-COVID-19 Accessed on 08 April 2021.  

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