5 Best Anti-COVID Nasal Sprays (2022)

Do nasal sprays actually work against COVID-19? There has been quite a lot of activities in the COVID nasal spray space. Below, we look at some of the best nasal sprays for COVID-19 and summaries of the rationale and evidence for each category. Do note that some of them are available as an over-the-counter medication but some are still under clinical trial stage.
 
McCullough et al. Reviews in Cardiovascular Medicine, 2020

Best Nasal Sprays for COVID-19 2022

There are lots of great nasal sprays out there, and this list is by no means complete. We’ve included nasal sprays with proven anti-COVID-19 ingredient, you can buy over the counter or online.

1. Xlear Nasal Spray (available on Amazon)

New research suggests an Xlear nasal spray is effective at significantly reducing and nearly eliminating SARS-CoV-2, the virus that causes COVID-19 after a single dose.

An in vitro study conducted by scientists from Northwestern University and Utah State University concluded that components found within the Xlear nasal spray, particularly grapefruit seed extract and xylitol, were successful in statistically reducing the amount of SARS-CoV-2.

After a single blast, the researchers saw the nasal spray reduced virus from 4.2 to 1.7 log10 CCID50 per 0.1 mL, a statistically significant reduction of 2.5 log10 CCID50.” News of the study was announced by Xlear and the company said this is only the latest research that reaches a conclusion the over-the-counter spray is effective against the virus that causes COVID-19.

Xlear is currently sold as a nasal irrigant for cleansing and moisturizing the nasal cavities.

Professor Mark Cannon of the Feinberg School of Medicine at Northwestern University said the study breaks ground in two areas. Cannon said using electron microscopy, the researchers saw visual evidence that showed the combination of xylitol and grapefruit seed extract counters the virus. The grapefruit seed extract kills the virus, while the xylitol prevents the virus from attaching to the cell walls, Cannon said in the announcement. The study postulates that xylitol acts as a decoy target for SARS-CoV-2, preventing virus attachment to the core protein on the cell wall, he said.

“In addition to countering SARS-CoV-2, Xlear is likely effective in preventing the spread of future H1N1 viruses, including the emerging SARS-CoV-2 variants, along with other viral epidemics. Given the more transmissible variants we now face, this is critical now,” Cannon said in a statement.

That in vitro evidence will no doubt be used to support a new petition before the World Health Organization. This week, a coalition of health professionals petitioned the World Health Organization to issue Guidance calling on: “all people to use nasal sprays to combat the COVID-19 pandemic.” The petition, which is supported by Xlear, is touting data that shows these nasal sprays are able to block viral adhesion and even kill or deactivate the virus in the nasal passages. The petition calls specifically for WHO Guidance to focus on the use of nasal sprays that contain Xylitol and grapefruit seed extract, which is found in Xlear.

“Nasal sprays are proven safe, inexpensive, non-invasive, easy to use and you can get them off-the-shelf at your local store around the world. There is a growing body of data that sprays, in particular Xlear, can help combat the COVID-19 pandemic. It’s pure commonsense,” Nathan Jones, chief executive officer of Xlear said in a statement.

In December, Xlear filed a Pre-Emergency Use Authorization request with the U.S. Food and Drug Administration in hopes of securing authorization of the spray as a new hygiene tool to help in combat the SARS-CoV-2 virus.

Xlear isn’t the only nasal spray that is showing promise in providing another level of protection against COVID-19, which has infected nearly 100 million people across the globe and led to the deaths more than 2 million people. Researchers from the University of Birmingham in the U.K. developed a nasal spray that can potentially provide protection against COVID-19. The spray uses compounds that are already approved by regulatory authorities in the UK, Europe and the U.S., including carrageenan, along with a gellan polysaccharide.

Another nasal spray that uses a lipopeptide, a cholesterol particle linked to a chain of amino acids, has also shown promise in preclinical testing. As BioSpace previously reported, the lipopeptide matches the stretch of amino acids in the spike protein of SARS-CoV-2 exactly. The lipopeptide attaches itself onto one of the spike’s amino acid chains and prevents viral attachment.


Where to Buy: Find Xlear on Amazon.

2. Saline Nasal Spray

A study, published in ACS Pharmacology & Translational Science (Sep 2021) proposing a simple prevention/treatment method that can be made/applied in just about any country, regardless of how poor and remote it is. Namely, a simple solution of salt in water, such that the concentration of salt is about 1.5% (e.g. commonly known as “hypertonic”) in the solution, had a 100% effectiveness of stopping SARS-CoV-2 replication.  

This effectiveness actually exceeds the results (90% inhibition) demonstrated by the study on low-dose vitamin E mentioned above. As the study says, this simple hypertonic saline solution can be administered as a nasal spray as a prophylactic method, or for treating early stages of the infection. For already established or more severe cases affecting the lungs, a nebulizer may have to be used so that the salt vapors can reach the lower regions of the respiratory tract. 

The mechanism of action for the anti-viral effects of the saline is remarkably simple – i.e. the extra salt from the solution accumulates into the cells, which forces them to expend ATP in order to re-balance the electrolyte gradient, and this limits the amount of ATP available for viral replication. Since virtually all viruses, including SARS-CoV-2, depend for their survival on being able to hijack ATP for their own replication this study suggests hypertonic saline may be a universally applicable antiviral treatment.

Saline Nasal Spray COVID-19 Studies and Updates: 

Feb 2, 2021 - Indian prospective controlled study (n=251) of saline nasal spray and gargle shows positive impact on PCR negativity and lung involvement. Many studies with different products now point to the very beneficial impact of that cheap, simple procedure.
Uday Chatterjee, Ajay Chakraborty, Sishir Naskar, Bibhuti Saha, Bhaswati Bandyapadhyay, Subhasis Shee.
Efficacy of normal saline nasal spray and gargle on SARS-CoV-2 for prevention of COVID-19 pneumonia.

July 2, 2021: Doctors at Pune's Deenanath Hospital claim traditional jalneti is helping them steer clear of COVID-19
“The COVID-19 virus gets lodged in the nostril. It has been found that a person tests positive on the fourth day after this happens. So, the virus seems to establish a colony during these four days. We are trying to wash out the virus and reduce the viral load on a daily basis via this method."
Jalneti is a yoga technique, in which sterilised and lukewarm isotonic salt water is poured into one nostril so that it leaves through the other.

Patients who initiated isotonic saline nasal irrigation after a positive COVID-19 PCR test were 19 times less likely to be hospitalized than the national rate. 

3. Povidone Iodine Nasal Spray and COVID-19

Povidone iodine (PVP-I) is an antiseptic that has been used for over 150 years. It's already proven that different concentration of PVP-I can deactivate COVID-19 virus. 

There are 12 published studies from 8 countries supporting povidone-iodine for COVID-19. You can check out the list and details on c19pvpi.com.

Povidone-iodine is no. 5 in this COVID-19 early treatment mortality drug league table:



Related: Betadine Gargle.

4. Sanotize (Nitric Oxide Nasal Spray) from Canada

The product is authorized as a medical device targeting COVID-19 in India, Israel, Bahrain, Indonesia and Thailand.

Canadian biotech SaNOtize’s nitric oxide nasal spray Enovid became available in pharmacies in Israel in July 2021 as a treatment for COVID-19. 

Enovid, a spray developed in Canada by SaNOtize and manufactured in Israel has been found to reduce viral loads in confirmed COVID-19 cases by 95% in 24 hours and 99% in 72 hours.

The spray received emergency use authorisation in Israel in early July 2021 after Phase II trials showed it reduces SARS-CoV-2 viral load, and therefore decrease a person’s transmission of the virus.

Releasing a small dose of nitric oxide, a natural nanomolecule with anti-microbial properties including against SARS-CoV-2, Enovid provides a physical and chemical barrier in the nose.

In June 2021, SaNOtize announced it had received approval from Health Canada to proceed with enrolment of volunteers in Phase III trials, and submitted an application for a New Drug Submission under Health Canada’s Interim Order.

 


Businesswire: UK Clinical Trial Confirms SaNOtize’s Breakthrough Treatment for COVID-19

In a randomized, double-blind, placebo-controlled Phase 2 trial that evaluated 79 confirmed cases of COVID-19, SaNOtize’s early treatment for COVID-19 significantly reduced the level of SARS-CoV-2, including in patients with high viral loads. The average viral log reduction in the first 24 hours was 1.362, which corresponds to a decline of about 95%. Within 72 hours, the viral load dropped by more than 99%. The majority of these patients had been infected with the UK variant, which is considered a variant of concern. There were no adverse health events recorded in the UK trial, or in over 7,000 self-administered treatments given in earlier Canadian clinical trials.

NONS is the only novel therapeutic treatment so far proven to reduce viral load in humans that is not a monoclonal antibody treatment. Monoclonal antibodies are highly specific, expensive and must be administered intravenously in a clinical setting.

“I expect this to be a major advance in the global battle against the devastating human impacts of the COVID-19 pandemic,” said Dr. Stephen Winchester, Consultant Medical Virologist and Chief Investigator of this NHS Clinical Trial. “This simple portable nasal spray could be highly effective in the treatment of COVID-19 and reducing onward transmission. Our trial included patients with a variant of concern and high viral loads yet still demonstrated significant reductions in the levels of SARS-CoV-2, which could be critical in supporting vaccines, preventing future outbreaks and safely reopening economies. Simply stated, I think this could be revolutionary.”

The SaNOtize treatment is designed to kill the virus in the upper airways, preventing it from incubating and spreading to the lungs. It is based on nitric oxide (NO), a natural nanomolecule produced by the human body with proven anti-microbial properties shown to have a direct effect on SARS-CoV-2, the virus that causes COVID-19. The pharmacology, toxicity, and safety data for NO use in humans has been well-established for decades. The NO molecule released from NONS is identical to the one delivered in its gaseous form to treat persistent pulmonary hypertension, or Blue Baby Syndrome, in newborn babies.

SaNOtize Seeking Emergency Use Authorization in UK and Canada

SaNOtize is applying to regulatory authorities in the UK and Canada for Emergency Use authorization. Swift approval and ramp-up of manufacturing could facilitate an almost immediate safe return to work, school and society, and spur an economic recovery that is months – if not years – ahead of full global vaccination.

Wide-scale equitable global availability of NONS could form a bridge during the global production and distribution of vaccines to help keep people safe and healthy. The ease of NONS manufacture, storage and use makes NONS a treatment candidate that could soon be widely available at low-cost for long-term care facilities, healthcare and frontline workers, and the general population.

In addition to providing antiviral treatment in the early stages of infection and for those who have yet to be vaccinated, NONS has also demonstrated that it could also reduce infectivity – the frequency of transmission from an infected person to a non-infected person.

The results of the UK trial corroborate the information gathered from SaNOtize’s earlier Phase 2 trials in Canada and independent lab tests at Utah State University’s Antiviral Research Institute.

“Now that NONS has been demonstrated to be safe and effective in clinical trials, we must move with urgency to get it into the hands of the public where it can help bring an end to the pandemic, accelerate a return to normality, and prevent future outbreaks of COVID-19 and its variants,” said Dr. Gilly Regev, CEO and co-founder of SaNOtize. “The human toll of this disease cannot be expressed simply in numbers, and each day compounds the frustration, fear and loss suffered by millions around the world. Combined with the roll-out of vaccines, NONS can help get the world back on its feet.”

Positive Phase 3 Study Results

In February 2022, the company reported a Phase 3 trial achieve its primary endpoint while demonstrating a reduction in SARS-CoV-2 log viral load in COVID-19 patients by over 94% within 24 hours of treatment. Within 48 hours the viral load was wiped out by 99%.

Moreover, a greater proportion of people in the high risk group, numbering 218, achieved a combination of clinical and virological cure, based on the WHO Progression Scale. They report a stunning medical time to virological cure at 4 days in the treatment group and eight days in the placebo group (p<0.05). Moreover, Glenmark Pharmaceuticals received manufacturing and marketing approval for the Nitric Oxide Nasal Spray (NONS) as part of an accelerated approval process.

Co-Founder and CEO Gilly Regev shared with TrialSite’s Founder Daniel O’Connor, “SaNOtize is excited to have Glenmark as our partner for manufacturing and distribution in India. We share the vision for this product and hoping it will become the first line of treatment and defence against respiratory viral infections.”

Where to Buy Sanotize Nasal Spray

Canadian biotech SaNOtize’s nitric oxide nasal spray Enovid became available in pharmacies in Israel in July 2021 as a treatment for Covid-19. You can purchase it online from IsraelPharm.com.

Glenmark Pharmaceuticals has signed a partnership with Canadian company SaNOtize Research & Development Corp., to manufacture, market and distribute Nitric Oxide Nasal Spray (NONS) for COVID-19 treatment in India and Asian markets including Malaysia, Singapore, Hong Kong, Taiwan, Brunei, Nepal, Cambodia, Laos, Myanmar, Sri Lanka, Timor-Leste and Vietnam.

5. Iota-Carrageenan Nasal Spray for COVID-19

Marinomed Biotech AG (VSE:MARI), an Austrian science-based biotech company with globally marketed therapeutics derived from innovative proprietary technology platforms, announced today that Carragelose inactivates the new, rapidly spreading variants and SARS-CoV-2 wildtype with similar efficacy in vitro. The Company tested the three variants that currently mostly drive the COVID-19 pandemic, namely the so-called British or B.1.1.7, the South-African or B.1.351, and the Brazilian or P1 variant.[*] The data demonstrate that also with increasing prevalence of virus variants, the marketed OTC Carragelose-based lozenges, nasal and throat sprays will continue to effectively contribute to combatting the COVID-19 pandemic.



“The COVID-19 pandemic continues to be a major health, social, and economic burden, and we now see variants of SARS-CoV-2 taking over the dynamics of the pandemic. We are very confident in these results that show Carragelose inactivates SARS-CoV-2, independent of the mutations we tested,” said Dr. Eva Prieschl-Grassauer, Chief Scientific Officer at Marinomed. “Given the broad antiviral efficacy and the physical mode of action, we were convinced that SARS‑CoV‑2 variants are unlikely to evade the antiviral efficacy of Carragelose. With these new results we confirmed the hypothesis that our Carragelose-based products continue to be effective also against the mutations of concern currently emerging strongly. We believe that this will hold true for any future variants.”

In recent in vitro tests, Marinomed included four lentiviruses differently pseudotyped with the spike protein of wild-type SARS-CoV-2 or one of the three variants B.1.1.7, B1.351 and P1, respectively. Carragelose was able to inactivate all four virus forms at concentrations below 5 µg/ml. This is clinically relevant for the use of Carragelose-containing products: The marketed nasal sprays have a Carragelose concentration of 1.2 mg / ml, a more than 200-fold higher dose as shown to be effective in vitro. The non-sulfated polymers HPMC and CMC were ineffective even at the highest concentrations tested.

In addition, two of the three SARS-CoV-2 variants (B1.1.7 and B1.351) were independently tested in Vero cell tissue culture in cooperation with the virological institute of the University Hospital Erlangen, Germany. Carragelose showed similar effectiveness against the SARS-CoV-2 wild type and the tested variants.

Dr. Prieschl-Grassauer continued: “We are very pleased to show that Carragelose is effective regardless of the actual SARS-CoV-2 variant. With the extensive discussions we are seeing around maintaining efficacy against a mutating virus, it is reassuring to know that Carragelose is a simple, safe, and effective means of supporting the prevention and treatment of COVID-19. With the data we have already seen against SARS-CoV-2 wild type, we are confident that this will hold true also for SARS-CoV-2 variants in the clinic.”

Marinomed’s lentivirus data show the ability of Carragelose to prevent the virus from attaching to the host cell. The infectious virus particles used in the cooperation with the virological institute of the University Hospital Erlangen mimic the effect of an actual infection, where the virus replicates in the host cells and then reinfects further cells, thereby spreading the infection in the body. Both are established and scientifically widely accepted models. Taken together, the data show how Carragelose can effectively inhibit SARS-CoV-2 variants in tissue culture. The cooperation partners plan to publish the data in a peer reviewed journal.

About Carragelose®:

Carragelose® is a sulfated polymer from red seaweed and is a unique, broadly active anti-viral compound. It is known as a gentle yet effective and safe prevention and treatment against respiratory infections. Several clinical and preclinical studies have shown that Carragelose® forms a layer on the mucosa wrapping entering viruses, thereby inactivating them, and preventing them from infecting cells. Increasing clinical evidence indicates that Carragelose® can also inactivate SARS-CoV-2.[1],[2] 

Marinomed is holder of the IP rights and has licensed Carragelose® for marketing in Europe, parts of Asia, Canada, and Australia. For a full list of Marinomed’s portfolio of Carragelose® containing nasal sprays and oral products, please visit https://www.carragelose.com/en/portfolio/launched-products, for a list of scientific publications on Carragelose®, https://www.carragelose.com/en/publications.


Related: BETADINE Cold Defence Nasal Spray (Amazon)

References:

[1] https://www.medrxiv.org/content/10.1101/2021.04.13.21255409v1.full.pdf
[2] https://www.marinomed.com/en/news/marinomed-biotech-ag-shares-positive-clinical-trial-results-for-iota-carrageenan-nasal-spray-in-the-prevention-of-covid-19-1


NB: COVID-19 is a highly dynamic topic. Please refer to the latest FLCCC protocol.

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