An in vitro study finds that nitric oxide may suppress SARS-CoV-2, the virus that causes COVID-19. The researchers suggest that inhaled nitric oxide may be an effective treatment for the disease.
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While the world awaits a clinically proven, widely available vaccine, there is an urgent need for more effective treatments for severe COVID-19 infections.
Currently, the only approved antiviral treatment for the infection is remdesivir, which can shorten recovery time for some people hospitalized with COVID-19.
A recent review of the research concludes that nitric oxide, a cell signaling molecule produced naturally by the body, could be a potential treatment for the new coronavirus.
The molecule has anti-inflammatory effects and is a vasodilator, meaning it dilates blood vessels to increase blood flow. It also has antiviral properties.
According to a 2005 in vitro study involving cell cultures grown in the lab, it also inhibits the replication of SARS-CoV. Closely related to SARS-CoV-2, this coronavirus caused the global outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003.
A small clinical study suggests that inhaled nitric oxide at low concentrations not only works as a vasodilator for SARS patients — improving oxygenation of their blood — but also as an antiviral agent.
An in vitro study that appears in the journal Redox Biology now provides the first direct evidence that nitric oxide also inhibits the replication of SARS-CoV-2.
Scientists at the Zoonosis Science Center at Uppsala University in Sweden conducted the research.
“Until we get a vaccine that works, our hope is that inhalation of [nitric oxide] might be an effective form of treatment,” says the senior author, Åke Lundkvist. “The dosage and timing of starting treatment probably play an important part in the outcome, and now need to be explored as soon as possible.”
To test nitric oxide’s antiviral effects, Lundkvist and his team used cultures of monkey cells infected with SARS-CoV-2.
They treated the cells with a chemical called SNAP (S-nitroso-N-acetylpenicillamine), which generates nitric oxide. As a control, they treated other infected cells with NAP (N-acetlypenicillamine), an almost identical chemical that does not produce nitric oxide.
SNAP reduced the amount of viral RNA produced by the infected cells and the damage inflicted by the virus. Increased concentrations of SNAP resulted in greater protection against the virus.
By contrast, NAP did not protect infected cells or reduce the amount of viral RNA they produced, confirming that nitric oxide was responsible for the antiviral effects.
The scientists were also able to show that nitric oxide inhibited a key enzyme called a protease that the virus needs to make copies of itself.
In theory, nitric oxide inhaled as gas could improve the outlook for patients with severe COVID-19.
Healthcare professionals already use inhaled nitric oxide to treat a range of heart and lung conditions.
In addition to antiviral effects, previous research suggests that it boosts the amount of oxygen in the blood by dilating blood vessels in parts of the lung where airflow is highest.
It also reduces blood clotting in the lungs, which is a particularly serious problem for COVID-19 patients who require ventilation.
Writing in their paper, the authors of the new study conclude:
“There is a great need for effective antivirals against SARS-CoV-2 in the ongoing COVID-19 pandemic. Based on this study and previous studies on SARS-CoV in vitro, and in a small clinical trial, we conclude that [nitric oxide] may be applied for clinical use in the treatment of COVID-19 and other human coronavirus infections.”
The new study involves treating infected cell cultures with a chemical that generates nitric oxide in situ.
The researchers are yet to prove that the gas has antiviral effects when inhaled, so they now plan to conduct further research in animal models of COVID-19.