8 Best Nasal Sprays for COVID-19 (2021)
Can you use a nasal spray for COVID? Do nasal sprays actually work against COVID-19? Below, we look at 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 for you to buy as an over-the-counter medication but some are still under clinical trial.
|McCullough et al. Reviews in Cardiovascular Medicine, 2020|
1. Nitric Oxide Nasal Spray (SaNOtize)
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.”
Double-Blind, Placebo-Controlled, Phase 2 Clinical Trial -- Details
This study, conducted by Dr Stephen Winchester and Dr Isaac John at Ashford and St. Peter’s Hospitals NHS Foundation Trust, was devised to determine the clinical efficacy of NONS for the treatment of mild COVID-19 infection. The primary outcome measure was the difference in SARS-CoV-2 RNA load from baseline through Day 6 between NONS and control arms.
“NONS destroys the virus, blocks entry into and halts viral replication within the nasal cavity, which rapidly reduces viral load. This is significant because viral load has been linked to infectivity and poor outcomes,” said Dr. Chris Miller, Chief Science Officer and co-founder of SaNOtize. “There is currently a lack of an antiviral therapy that is effective against COVID-19 and its variants, can prevent or shorten the course of the disease, reduce damage, lower the severity of COVID-19, and can be made widely and readily available to the public. This is what makes NONS unique and enables it to stand alone from any other novel therapeutic application.”
The study concluded that NONS accelerated clearance of SARS-CoV-2 by a factor of 16-fold versus the placebo, and it presents supporting evidence for the emergency use of NONS for prevention or treatment of patients with recent or established SARS-CoV-2 RNA infection during this COVID-19 pandemic.
“The rigour of this trial and the decades of safety data behind nitric oxide gives us full confidence in requesting emergency use approval in the UK, Canada and elsewhere in the world.” said Rob Wilson, SaNOtize’s UK representative. “We are pleased to have conducted this crucial trial in the NHS and now hope that regulators will play their part in arming the public in the battle against this devastating disease.”
2. Iota-Carrageenan Nasal Spray for COVID-19
|Iota-carrageenan nasal spray Amazon|
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.
3. Povidone Iodine and COVID-19
Povidone Iodine COVID-19 Studies
We have compiled a list of povidone iodine COVID-19 studies below:
Feb 2021 - Guenezan et al., JAMA Otolaryngol Head Neck Surg., doi:10.1001/jamaoto.2020.5490 (Peer Reviewed)
Povidone Iodine Mouthwash, Gargle, and Nasal Spray to Reduce Nasopharyngeal Viral Load in Patients With COVID-19: A Randomized Clinical Trial
RCT of PCR+ patients with Ct<=20 with 12 treatment and 12 control patients, concluding that nasopharyngeal decolonization may reduce the carriage of infectious SARS-CoV-2 in adults with mild to moderate COVID-19. All patients but 1 had negative viral titer by day 3 (group not specified). There was no significant difference in viral RNA quantification over time. The mean relative difference in viral titers between baseline and day 1 was 75% [43%-95%] in the intervention group and 32% [10%-65%] in the control group. Thyroid dysfunction occurred in 42% of treated patients, with spontaneous resolution after the end of treatment. Patients in the treatment group were younger.
Dec 2020 - Choudhury et al., Bioresearch Communications, Volume 7, Issue 1, January 2021 (Peer Reviewed)
Effect of 1% Povidone Iodine Mouthwash/Gargle, Nasal and Eye Drop in COVID-19 patient
RCT 606 patients in Bangladesh for povidone iodine mouthwash/gargle, nasal drops and eye drops showing significantly lower death, hospitalization, and PCR+ at day 7.
In Vitro Efficacy of a Povidone-Iodine Nasal Antiseptic for Rapid Inactivation of SARS-CoV-2
In Vitro study showing povidone-iodine nasal antiseptics at concentrations (0.5%, 1.25%, and 2.5%) completely inactivated SARS-CoV-2 within 15 seconds of contact. No cytotoxic effects on cells were observed after contact with each of the nasal antiseptics tested.
4. AeroNabs Nasal Spray for COVIDLed by graduate student Michael Schoof at Dr. Peter Walter’s lab in the UC San Francisco Department of Biochemistry and Biophysics, the team engineered antibodies from camelids to immobilize SARS-CoV-2, the virus responsible for COVID-19. Known as “AeroNabs,” these nanobodies provide a promising, immediate therapeutic treatment for COVID-19 illness before vaccines become widely accessible.
“Vaccination is critical, but it may take years before the whole world can get vaccinated,” Michael said. “So throughout that process and even after you still want a therapeutic treatment or post exposure prophylactic to be available.”
AeroNabs have several advantages over traditional therapeutic antibodies. AeroNabs are made of smaller, more stable camelid-derived antibodies (nanobodies) rather than typical antibodies. Therefore, these molecules are inexpensive to mass produce in bacteria or yeast, and they are stable to transport in the form of powders. Furthermore, AeroNabs can be easily aerosolized and self-administered with a nasal spray or inhaler.
The research team has recently completed testing AeroNabs on hamsters and are working their way to get AeroNabs into the clinics as the world is concentrated on developing vaccines and traditional antibodies. The team is also continuing to develop more versions of AeroNabs to target newly emerged variants of viral SARS-CoV-2.
Graphic courtesy of Cai Y; et al. Science, 2020, 369, 1586-1692.
“As the dynamics of the virus change over the coming year, especially that there’s a new potential pandemic continues to emerge, you can image there’s a version of virus really resistant to vaccine effort and there’s a new version of vaccine that only provides 50 percent effectiveness, I think options like this [nanobody treatment] become far more important [in this situation],” said Dr. Aashish Manglik, the co-principal investigator of the project.
The virus SARS-CoV-2 attacks a target lung cell by latching its spike protein to fit perfectly onto the human protein receptors, ACE2, which cover the surface of the cell. It is only after this interaction that the virus is able to enter the human cell and forcibly direct it to spread the viral RNA, causing a cascade of cell infection. However, with the AeroNabs developed by the UCSF team, this chance is greatly reduced because the virus binding with ACE2 is blocked by its binding to these nanobodies — an immune agent designed with a greater affinity to SARS-CoV-2.
“Antibody” is a general name for proteins that defend against foreign objects such as pathogenic bacteria and viruses in a host animal. Unlike the traditional antibodies found in mammals, these single-domain antibodies (nanobodies) originated from camelids, such as llama and alpacas, and are missing the light chain of a typical antibody, resulting in a simpler and more stable structure to engineer. Recently developed nanobody technology took advantage of these structural properties to expand nanobody applications in medicine and therapeutics.
Graphic courtesy of R&D Systems.
The original discovery of nanobody by Belgian biology professor Raymond Hamers in the late 1980s was unexpected. After finding a sample of carmel serum in the lab, Hammers assigned his undergraduate students to work on isolating antibodies from the sample. After purification, they discovered undocumented mini-antibodies. Further characterization revealed that these mini-antibodies belonged to a new class which they named “nanobodies”. Since Nature published this finding in 1993, nanobody technology has made notable progress in its application. For example, the FDA approved its use in treating a rare blood clotting disorder in 2019. This new biotechnology attracted many labs to employ it as a tool to develop therapeutics. Among them is Manglik’s lab at UCSF.
Manglik spent the past three years building the world’s largest library of nanobody DNA sequences with Dr. Andrew Kruse at Harvard Medical School. The library houses over two billion nanobody-expressing yeast cells. This powerful resource not only saves the time-consuming labor of harvesting nanobodies from the blood of llamas or camels, it’s also shared with the world to give hundreds of labs access to studying nanobodies.
“My lab normally studies something completely different, we are very interested in the receptors that enable our bodies to see, smell and taste,” Manglik said. “In order to study these receptors, we developed in the past these little antibodies to push and pull and manipulate these receptors to function.”
Walter and Manglik already teamed up before their project on tackling coronavirus with nanobodies. As a fourth year graduate student in the Walter lab, Michael specialized in studying the regulation of a protein named “eIF2B,” which is essential for protein translation and appears to be a critical regulatory hub during traumatic brain injury and other neurological disorders. Walter saw the potential application of nanobodies in modulating the behavior of eIF2B, and the partnership was soon made.
When COVID-19 surged through America in early 2020 and most non-COVID related research was closed down, the Waler lab promptly switched its gears to research SARS-CoV-2 with Manglik for a solution: Can nanobodies effectively halt the spread of the virus?
“Michael really took the lead on using some of the expertise he gained from my lab to find nanobodies against the spike protein,” Manglik said regarding their collaborative project on COVID-19.
The team screened through Manglik’s yeast surface-display library to narrow down the population that would likely bind to SARS-CoV-2 spikes. Within three weeks, they identified 800 potential candidates. Michael mixed these individual yeast cultures with fluorescently labeled SARS-CoV-2 Spike and excess human ACE2 protein. The preliminary result showed many nanobody expressedexpressing yeast, but the 21 top candidates showed competition with the ACE2 protein. These nanobodies were later classified into two types. Class 1 nanobodies, namely Nb6 and Nb11, competed directly with ACE2 for the same binding site on the spike, and Class 2 nanobodies such as Nb3 targeted a different domain. As both classes revealed decreased binding activity in the presence of increased ACE2, this classification would allow the team to identify the most potent candidate and engineer an ultrapotent version of itself.
The task was split among researchers, including biochemists and virologists across the campus and globe. The team collaborated with the QCRG Structural Biology Consortium to image the interaction between Nb6 and SARS-CoV-2 Spike using atomic-resolution cryo-electron microscopy. This data provided critical information about how Nb6 blocks ACE2 binding and allowed the team to further optimize the molecule into Nb6-tri by linking three Nb6 nanobodies with flexible linkers of amino acids — the basic structural unit of a protein.
“We have made the nanobodies look more like a human antibody through a humanization process,” Michael said. “It’s purely interacting with the viral protein and unlikely to have side effects.”
To examine its efficacy, Manglik connected with former UCSF postdoc Marco Vignuzzi to test Nb6-tri against live virus at his Biosafety Level 3 (BSL-3) laboratory located at Institut Pasteur in Paris. The result proved that this three-armed nanobody binds exceptionally well to SARS-CoV-2, making it a promising antiviral.
“Our thought is not to unnecessarily compete with the vaccine already deployed right now,” Manglik said. “It’s really to think about where an approach like this [nanobody] can have some utility.”
Months of work condensed into a paper published in Science last December. More than 50 researchers co-authored to propose the effective treatment of using this synthetic nanobody to inactivate SARS-CoV-2.
5. Taffix Nasal Spray for COVIDAn Israeli biopharmaceutical company developing powder-based intranasal products announced this week that a spray made by the firm proved highly effective in lab tests against two prominent coronavirus variants, according to the findings of a new study. The spray was previously found to effectively reduce the spread of SARS- CoV-2, the virus that causes COVID-19, in a real-world trial last year.
Nasus Pharma said that in a new collaborative study with the Central Virology Laboratory at the Israeli Ministry of Health and the Sheba Medical Center at Tel Hashomer Hospital, the company’s proprietary Taffix spray “blocked 100 percent” of the two new variants of SARS-CoV-2 virus, the British variant, also known as B.1.1.7, and the South African variant.
The British variant was found in a new study at Tel Aviv University to be 45 percent more contagious than the original virus.
In the in vitro study by Nasus, the gel layer produced by Taffix in a tissue culture infected with doses of the virus variants was effective at blocking them, as demonstrated by PCR testing of the cells.
The company did not give further details about the study nor did it indicate when it was conducted, whether the findings were published, or whether further studies were in the offing.
Nasus Pharma CEO Dr. Dalia Megiddo said in a statement that the results “conform with prior in vitro studies performed with Taffix where 99.99 percent of SARS- CoV-2 viruses were blocked by Taffix, as well as other viruses known to cause upper respiratory infections.”
Nasus said that it is now well established that the nasal cavity is the main gateway to the body of airborne droplet viral infection including SARS-COV-2, and the Taffix powder creates a thin acidified gel above the nasal mucosa that shields the nasal cells from inhaled viruses through both mechanical and chemical protection. The gel lasts five hours and could be used as an additional layer of protection against infection, Nasus Pharma indicated.
The results of the latest study, said Dr. Megiddo, are “consistent with real-life clinical experience with Taffix where the risk of contracting COVID was reduced by 78 percent following a ‘super spreader’ event.”
Dr. Meggido is referring to a separate study last year during Rosh Hashanah where the spray appears to have contributed to a reduced COVID-19 infection rate among ultra-Orthodox members of a synagogue in Bnei Brak.
At the time, in September 2020, Israel was a world leader in the number of new COVID-19 cases per one million citizens and the rate of infection in ultra-Orthodox communities was double. The mortality rate was also higher. Before Rosh Hashanah, Bnei Brak’s positivity rates for COVID-19 were 17.6 percent, climbing to 28.1 percent two weeks later, the study showed.
Ahead of the approaching holiday, characterized by mass gatherings at synagogues for prayers and family events, there were concerns about such events becoming sources of mass outbreaks. Nasus approached a synagogue community of 243 members in Bnei Brak and made available bottles of the spray to use during the holiday and thereafter.
A total of 83 worshipers used the spray before Rosh Hashanah prayers and for the following two weeks according to instructions, and just two contracted the virus in a real-world test of the product, the company said. The two who contracted the virus did not use the spray as instructed and the remaining members did not use the spray at all, according to surveys conducted for the study.
That study was conducted in partnership with scientists from the University of Haifa, the University of Virginia, and the Hadassah Medical Center in Jerusalem. Preprints were available in November 2020 and in January 2021, and the full study was published after peer-review in recent weeks.
“Given the excellent safety profile of Taffix and its statistically significant efficacy in preventing infection following what is defined as high-risk infection event — it seems that this additional layer of protection can significantly reduce the risks of infection and may enable people to resume some part of their daily routine more safely,” the authors of the study wrote. They called for controlled clinical trials to more precisely define target populations and means of encouraging adherence.
Professor Yaakov Naparstek, the scientific director of the Meuhedet HMO Research Institute and a physician at Hadassah Medical Center who co-authored the study said that “the fact that Taffix was able to significantly reduce infection rate in users of the product is very encouraging.”
“The study’s results reconfirm the versatility of our technology against various respiratory viruses including SARS-CoV-2 and its new variants and Taffix’s potential as an important additional layer of protection against infection,” she added.
“Our new data demonstrates that Taffix can be helpful in preventing the spread of these new variants in addition to all other recommended safety measures,” he said.
Taffix is available in Israel and is also currently sold in over 20 countries across Europe, Latin America, Asia and Middle East, the company said.
Nasus Pharma is based in Tel Aviv and is also developing a number of intranasal products aimed at assisting patients in several acute emergency situations such as opioid overdose and anaphylactic shock.
It is not the only company in the market touting a spray-based solution to fighting COVID-19 infection. SaNOtize (see above), the company behind a proposed antiviral nasal spray for use against COVID-19 has started a production line in Israel where the Health Ministry gave its interim approval for the sale of the product to people over 12 years of age.
The company, co-founded by Israeli-Canadian scientist Dr. Gilly Regev and based in Vancouver, developed a patented platform technology that allows for the topical delivery of nitric oxide (a naturally occurring nanomolecule with the formula NO, hence the name) to treat a variety of bacterial, fungal, and viral diseases.
The company’s Nitric Oxide Nasal Spray (NONS), under the brand name Enovid, is designed to kill SARs-CoV-2, the virus that causes COVID-19, in the upper airways, preventing it from incubating and spreading to the lungs. The spray is undergoing clinical trial in the UK and is currently in Phase II prevention and efficacy trial in Canada.
6. Xlear Nasal SprayNew research suggests an over-the-counter 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.
7. Halberd COVID-19 Preventative Nasal Spray
The nasal spray is intended to be used as a prophylactic against contracting Covid-19 specifically, and coronaviruses in general. The mechanism of action utilizes an antibody with a solution which blocks ACE2 receptors found in nasal epithelial cells. The nasal spray may possibly decrease the severity of clinical manifestations in infected patients by decreasing the initial Covid-19 viral load.
The technology covered in this provisional patent application is fully compatible with Halberd's current research and extends it to address all three phases of the coronavirus:
- A Preventative and Early Treatment;
- A Diagnostic, and
- A Therapeutic Treatment.
Mr. William A. Hartman, Chairman, President & CEO of Halberd Corporation, stated, "We continue to closely monitor technology advancements, across all of our sites, in the fight against Covid-19 and develop products to address the most pressing needs. We continue to make progress towards this goal."