10 Best Nasal Sprays for COVID-19 (2023)
Do nasal sprays actually work against COVID-19? Can I use nasal spray if I have COVID-19?
The COVID-19 pandemic has been roaring on for 3 years. During this time, the FDA has authorized many treatments that help combat COVID-19. COVID-19 vaccines have also been recommended by the CDC ever since the first ones were authorized in December 2020.However, medications that are already authorized are just a small percentage of what's been studied. Many researchers are still trying to find and develop other medications that can treat or prevent COVID-19.
Among these, nasal sprays have caught the attention of many people. They’re often easy to use, and some researchers believe they could have a potential impact on the ongoing pandemic. But are any of them effective at treating or preventing COVID-19? And are any of them close to being available in the U.S.?
Which nasal sprays have been studied to treat or prevent COVID-19? A number of nasal sprays are being developed or repurposed in an attempt to treat people who have tested positive for COVID-19. And even though they wouldn’t be a substitute for COVID-19 vaccines, some are also being studied to help prevent the illness.
Best Nasal Sprays for COVID-19
1. Povidone Iodine Nasal Spray and COVID-19Povidone iodine (PVP-I) is an antiseptic that has been used for over 150 years. The antiseptic has immediate virucidal effects against COVID-19 virus. Do we have any evidence that povidone iodine is effective against COVID-19?
The group of patients used 1% PVP-I [One per cent Povidone Iodine Solution] have shown tremendously reduced mortality, morbidity and hospital as well as financial burden in this covid situation.
2. Xlear Natural Saline Nasal Spray with Xylitol (Available on Amazon)
“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 March 2021, 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.
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.
So far, this type of research has been influential in some countries. For instance, one nitric oxide nasal spray — called Enovid — is already available in Israel and on Amazon.com.
Canadian biotech SaNOtize’s nitric oxide nasal spray Enovid became available in pharmacies in Israel in July 2021 as a treatment for Covid-19.
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.
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.
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.
4. Saline Nasal Spray and Irrigation
5. Iota-Carrageenan Nasal Spray for COVID-19
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.
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.
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.
-  https://www.dovepress.com/efficacy-of-a-nasal-spray-containing-iota-carrageenan-in-the-postexpos-peer-reviewed-fulltext-article-IJGM
-  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
- A Seaweed Nasal Spray May Combat COVID
6. Nasal spray vaccinesA number of COVID-19 nasal spray vaccines are also being researched and developed. It’s thought that they could help build up protective antibodies in your nose that fight SARS-CoV-2.
China has become the first country to approve an inhaled Covid vaccine. Made by CanSino (“CanSinoBIO”) (SSE: 688185, HKEX: 06185), Convidecia Air has similar ingredients to its injected vaccine, using a harmless adenovirus as a carrier for the genetic code that teaches the body how to fight Covid. It can top up protection in those who have previously had a jab, trials suggest.
7. Steroid nasal spraysCorticosteroid (steroid) nasal sprays are available widely in the U.S., and they’re often used for treating conditions like allergies and nasal polyps. But some researchers are exploring their potential as a treatment option for COVID-19. It’s thought that these sprays can help control inflammation while also stopping the coronavirus from entering your respiratory system.
In one Cleveland Clinic study, registry data from over 70,000 people with mild-to-moderate COVID-19 was collected. Results suggested that corticosteroid nasal sprays may help prevent hospitalizations, ICU admissions, or death from COVID-19. But to see if they’re truly safe and effective for COVID-19, clinical trials would need to be performed.
Related: Inhaled Budesonide and COVID-19
8. 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.
“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.
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.
9. Taffix Nasal SprayAn 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 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.
10. BioBlock®, a Prophylactic Nasal Spray With Antibodies Against SARS-CoV-2
BioBlock® is a natural product derived from bovine colostrum collected from cows hyperimmunized with the SARS-CoV-2 viral spike protein. Bovine colostrum is milk produced by cows within the first few days after giving birth that contains antibodies that provide passive immunity to the newborn calves. BioBlock® is produced from colostrum that, along with other naturally occurring beneficial antibodies, contains antibodies against SARS-CoV-2.
"It is a natural product sprayed into the nasopharynx, with a single administration dose containing 80 mg of bovine antibodies, which is 2,000 times less than in one glass of milk," professor Ustav specified. However, it should be noted that, although BioBlock® is lactose-free, it is not recommended for people with allergies to milk proteins.
Furthermore, according to professor Ustav, tests have shown that these antibodies are not only effective against the first virus strain that originated in Wuhan, but also against the new, more prevalent virus variants from Great Britain (B.1.1.7), South Africa (B.1.351), and Brazil (P.1). It was studied both in biochemical and in BSL-3 laboratory live SARS-CoV-2 virus experiments at the University of Tartu, which confirmed its broad activity. Effectiveness against the Indian strain of the virus is currently being tested and determined.
A clinical study has shown that the antibodies in BioBlock® nasal spray remain on the mucosa and provide protection for up to 4 hours.
BioBlock® could be helpful as an additional preventive measure against the SARS-CoV-2 virus whenever or wherever social distancing is difficult and potential risk for infection is present—at home or work, in restaurants, schools, gyms, public transportation, or other crowded places.
Consortium of Estonian companies
To develop, produce, and bring to the market the novel BioBlock® nasal spray, a number of well-established Estonian companies and universities joined together to form a consortium. The consortium includes the following: Icosagen Cell Factory OÜ; AS Chemi-Pharm; OÜ Teadus ja Tegu; Estonian University of Life Sciences (Institute of Veterinary Medicine and OÜ Eerika farm); and University of Tartu (Institute of Pharmacy, Institute of Biomedical and Translational Medicine, and Institute of Technology).
Collectively, members of the consortium including Icosagen Cell Factory OÜ, Chemi-Pharm AS, and the Institute of Pharmacy of the University of Tartu have developed a precise recipe for BioBlock® that ensures efficacy and safety of the product.
"Production volumes are growing every week, reaching hundreds of thousands in the coming months. In particular, we supply nasal spray to Estonian residents in Benu pharmacies and Chemi-Pharm e-store. The next step is to plan exports to neighboring countries first, then further afield,” said Ruth Oltjer, the founder of Chemi-Pharm.
BioBlock® nasal spray is marketed under the new Chemi-Pharm brand Medihex. BioBlock® is currently restricted to sale in Estonia.
What medications can I take to treat or prevent COVID-19?Nasal sprays aside, many medications are already authorized to treat and prevent COVID-19. Your healthcare provider can tell you if you’re eligible to access any of these treatments.
Medications that can treat COVID-19 if you aren’t in the hospital
- Paxlovid (nirmatrelvir and ritonavir), an oral tablet
- Veklury (remdesivir), an intravenous (IV) infusion
- Lagevrio (molnupiravir), an oral capsule
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