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

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.