Nitric Oxide and its Derivatives Containing Nasal Spray and Inhalation Therapy for the Treatment of COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major health concern worldwide and has evolved into different variants. SARS-CoV-2 possesses a spike glycoprotein on its envelope that binds to the angiotensin-converting enzyme 2 (ACE-2) receptor of the host cell via the receptor-binding domain (RBD) in the upper respiratory tract. Since the SARS-CoV-2 virus variants change the severity of the diesease and treatment scenarios, repurposing current medicines may provide a quick and appealing method with established safety features. The efficacy and safety of antiviral medicines against the coronavirus disease 2019 (COVID-19) have been investigated, and several of them are now undergoing clinical studies. Recently, it has been found that nitric oxide (NO) shows antiviral properties against SARS-CoV-2 and prevents the virus from binding to a host cell. In addition, NO is a well-known vasodilator and acts as an important coagulation mediator. With the fast-track development of COVID-19 treatments and vaccines, one avenue of research aimed at improving therapeutics is exploring different forms of drug delivery, including intranasal sprays and inhalation therapy. The nasal mucosa is more prone to be the site of infection as it is in more direct contact with the physical environment via air during inhalation and exhalation. Thus, the use of exogenous nasal NO therapy via the intranasal route displays a distinct advantage. Therefore, the objective of this review is to summarize the relevant actions of NO via the intranasal spray and inhalation delivery, its mechanism of action, and its use in the treatment of COVID-19.