Till date, there is still no specific drug for controlling Covid-19. While scientists worldwide are working on effective antiviral drugs against SARS-CoV2, some are looking beyond drugs. For example, a multinational collaboration has recently announced results of phase 2 clinical trials indicating that a nitric oxide nasal spray can be an effective viral treatment. It is not, however, the first time nitric oxide has been studied as a therapy for infection or other illnesses.
What is this therapy?
Nitric oxide is known to have a broad antimicrobial effect against bacteria, fungi, helminths, protozoa and viruses. To assess the potential of NO as a treatment for SARS-CoV-2 infection, researchers evaluated its vitro antiviral effect on SARS-CoV-2 replication and published their findings in September 2020. (‘Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro’, Redox Biology)
Prof Ake Lundkvist of Uppsala University, Sweden, one of the authors of the paper, has said, “To our knowledge, nitric oxide is the only substance shown so far to have a direct effect on SARS-CoV-2”.
And what is this spray?
It has been developed by a Vancouver-based biotech firm, SaNOtize Research and Development Corporations, along with St Peter’s hospitals, NHS Foundation Trust in Surrey, and Berkshire and Surrey Pathology Services. “The spray releases a small, topical amount of nitric oxide that is well known to kill viruses including SARS-CoV-2. It is non-specific and thus kills any virus,” said Dr Gilly Regev, CEO and co-founder of SaNOtize.
What were the trial results?
It was a randomised, double-blinded, placebo-controlled phase 2 trial. It evaluated 79 confirmed cases of Covid-19.
According to the announced results, early treatment helped reduce the level of SARS-CoV2. Patients treated with the spray saw an average reduction of around 95% in viral load in the first 24 hours, and more than 99% within 72 hours. No side effects or adverse events were observed.
A majority of the patients had been infected with the variant first detected in the UK, Dr Stephen Winchester, consultant medical virologist and chief investigator of NHS clinical trials, told The Indian Express by email.
With the virus airborne, how long does the effect of the spray last?
“It is a ‘post-exposure’ prevention — just like the hand sanitiser is,” said Dr Chris Miller, Chief Science Officer at SaNotize.
The self-administered nasal spray releases a small topical amount of nitric oxide and aims to kill the virus in the upper airways, preventing it from incubating and making its way to the lungs. Dr Miller said: “If you are outside, around people, and could be infected, you could use the spray and reduce the number of viruses in the nose, before it is becoming a full-blown infection. We have shown that even when people have a very high load of virus, the spray can significantly reduce the viral load.”
Has it got any kind of clearance?
The World Health Organization has yet to give an emergency use authorisation (EUA). According to Dr Regev, Israel and Bahrain have given EUA to the spray, as a medical device. The developers have also applied for EUA in the UK, Dr Winchester said.
A phase 3 trial is being planned, although it would be for regulators to decide if it was needed, Dr Winchester said.
According to Dr Regev, the developers are in discussions with some pharmaceutical companies in India.
How do scientists in India view this?
Prof Ram Vishwakarma, Advisor, Council of Scientific and Industrial Research (CSIR), said that as a scientist he was open to these developments. And Indian companies too are working on similar ideas.
“We are discussing several new developments daily. Scientifically it is an interesting idea and they have interesting phase 2 clinical trial results but not yet published in peer-reviewed journals to my knowledge. We are all waiting for the regulator to take a call — several Indian companies have started working on similar ideas,” said Prof Vishwakarma, who is the Chairman of the Covid strategy group of CSIR.
“There is no unequivocal data on antiviral activity of nitric oxide per se — I have seen the report and results. They are not the first company and several trials are underway worldwide,” he said.
What are these trials looking at?
Several molecules are in clinical trials, and at CSIR, too, there are 15 molecules in the preclinical stage of development. One or two may go into clinical trials in a few months, Prof Vishwakarma said.
“We will need therapeutics for this virus and also develop more monoclonal antibodies . This RNA virus is different and it is too short a time for people to develop new drugs. Hence several drugs have been repurposed,” he said. “Regarding the nasal spray, this is a formulation where NO can be slowly released… There are clinical trials happening where doctors are testing if the tiny amounts of NO gas can be given to the patient so he/she can breathe better. It relaxes blood vessels.”