Nitric oxide, with the molecular formula of NO, is a gaseous molecule that is emerging as a central regulator of energy metabolism and many immune system functions inside the human body. It carries out integral physiological functions as a part of multiple systems inside the body.
With the current pandemic hitting hard on many countries around the world, the rising death toll warrants search for an effective treatment. The novel coronavirus that originated in the Wuhan city of China has symptoms ranging from mild upper respiratory symptoms to severe diffuse viral pneumonia with simultaneously occurring multi-organ failure leading to death.
Nitric oxide, because of its special function as a part of the host defense system inside the body and a significant role in the mediation of innate immune response against viral pathogens, has become the center of attention of many research facilities. As all the scientists and healthcare professionals around the world face the dilemma of no known trgeted treatment and vaccine for this novel COVID-19, the efforts are being maximally put in figuring out all the factors and chemical compounds that impact the overall immunity inside the human body.
How Nitric Oxide Boosts Immunity
Nitric oxide is an important molecule produced inside the human body whose synthesis is a vital biochemical process involving nitric oxide synthase (NOS) enzyme family. It has been established that the phagocytes, monocytes, and macrophages which take part in the physiological immune response, the innate or nonspecific immune response, inside the body have this NOS enzyme. There are three known types of NOS: constituent or calcium-dependent isoforms that are primarily present in the endothelial cells and neuronal cells (eNOS and nNOS) and the inducible or calcium-independent isoform (iNOS). The isoform that lines the respiratory system can perform multiple functions which may be the inducible nitric oxide synthase (iNOS) type especially in the case of immunologic response. The activity of this enzyme has been seen in a variety of microbial infections. This enzyme is stimulated by interferon-gamma (IFN-gamma) which commences the production of nitric oxide by these white IL-10 and transforming growth factor-beta (TGF-β) are released by type 2 helper T cells. Therefore, the production and release of nitric oxide from the inducible nitric oxide synthase enzyme is fairly regulated. In response to any microbial, viral and parasitic attack nitric oxide is released by the phagocytes, macrophages and other fighting white blood cells as a part of the body’s immune response.
In this antiviral response to some specific DNA and RNA viruses pathogens attacking the respiratory system, the iNOS inside the type 2 alveolar cells become activated and the production of nitric oxide begins. NO further induces its immunologic response against viral pathogens by directly contributing to the oxidative stress and imparting oxidative injury to the tissues in processes such as host cell apoptosis and necrosis acting as scavengers. Because of this, a high concentration is produced during an inflammatory response to any pathogen that attacks the body from outside. As a result of this response, NO serves as an inflammatory meter which is measured as a breath test in diseases where airway inflammation has occurred due to any stimulant.
Nitric Oxide for Coronavirus
NO has always been known as a potential therapeutic agent in the treatment of acute as well as chronic respiratory tract infections. It has been known to kill bacteria as well as inhibit the replication of viruses, both DNA and RNA type viruses. The inhibitory effect of nitric oxide on viruses has led to a belief that nitric oxide may show some success in dealing with the highly contagious coronavirus. NO has been found to act on multiple steps in the process of replication. The step of protein coat synthesis, as well as RNA replication, are all disintegrated by the nitric oxide molecule. It does this by targeting the molecules essential for these procedures and modifies them. These two important steps produce new genome copies and new coats for the new virion being generated for continuing the process of infection. A drug that was previously known to dilate the blood vessels has helped recover some patients suffering from severe lung damage when taken by inhalation.
In the previous SARS outbreak, which is another strain from the same family as COVID-19, NO administration to the patient showed an improvement in the overall functioning of the respiratory system. This mixture of nitric oxide (0.8%) and nitrogen (99.2%) reduced hypoxia and improved blood circulation due to dilatation of the blood vessels, which ultimately shortened the length of the ventilatory support that these patients needed in comparison to the patients who were not exposed to any NO mixture inhalation.
To top it off, in all the experimental data collected so far NO has shown maximum benefits with minimum risks and side effects when it was administered as a part of the treatment regimen in early phases of the course of infection which may even prevent the progression of the disease to acute respiratory distress or multi-organ failure.
The role of nitric oxide in working against the coronavirus replication fairly early in the course of infection has proven that this may open a new avenue in the search for the treatment of this pathogen. Further investigations and research are still required to demonstrate the level of NO that needs to be administered in order for it to prove to be beneficial instead of harmful for the human body. A comprehensive understanding of the physiological and pathophysiological functions mediated by nitric oxide during a host defense response can further benefit the ongoing search into a better management regimen for the current biological war that befalls the whole world. If this inhalational treatment proves to be successful with every research and experiment, this can remarkably improve the survival rate without overburdening the already scarce ventilatory support provided by the healthcare system across the world.
- Tripathi P. Nitric oxide and immune response.
- Moilanen E, Vapaatalo H. Nitric oxide in inflammation and immune response. Annals of medicine. 1995 Jan 1;27(3):359-67.
- Åkerström S, Mousavi-Jazi M, Klingström J, Leijon M, Lundkvist Å, Mirazimi A. Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus. Journal of virology. 2005 Feb 1;79(3):1966-9.
- Clancy RM, Amin AR, Abramson SB. The role of nitric oxide in inflammation and immunity. Arthritis & Rheumatism. 1998 Jul;41(7):1141-51.
- Keyaerts E, Vijgen L, Chen L, Maes P, Hedenstierna G, Van Ranst M. Inhibition of SARS-coronavirus infection in vitro by S-nitroso-N-acetylpenicillamine, a nitric oxide donor compound. International journal of infectious diseases. 2004 Jul 1;8(4):223-6.
Written By Dr. Sung Won, MD & NeoGen Clinic Scientific Advisory Board Members