ANTI-COVID19 Nasal spray research by Dr. Disha Trivedi, MVS Pharma

Published at: 21.03.2022 08:47

ANTI-COVID19 NASAL SPRAY RESEARCH
By Dr, Disha Trivedi, MVS Pharma

[1]Covixyl-V 

Company Name: SALVACION USA Inc., Englewood Cliffs NJ

Active Compound: The active substance of Spray Covixyl-V is  Ethyl LauroylArginate Hydrochloride (ELAH) which is listed as a Generally Recognized as Safe (GRAS) ingredient by Food and Drug Administration (FDA) as safe to use in food and other over-the-counter products in the US, EU, UK and Germany.

Mechanism of Action:

COVIXYL-V works via blocking the virus at the nasal tissues and removing it (if the virus does not attach, it is washed away by mucous secretions.) It helps naturally remove the inactivated virus by blowing the nose or in normal nasal secretions.

Clinical Research:

In vitro study with rVSV-SARS-CoV-2 model showed that the virus is 99.99% inhibited at low concentration. In vivo study with Syrian hamster model, the same model Pfizer and Modena used for vaccine development, performed by BSL-3 laboratory demonstrated that COVID-19 is 99.99% inactivated with no adverse events found following the administration.

Three steps for usage:

Step 1. Spray: Apply 2-3 sprays at each nostril.

Step 2. Block: The unique formula with ELAH (Ethyl LauroylArginate HCL) blocks viral attachment to the nasopharynx and helps prevent the virus from developing and spreading.

Step 3. Remove: Due to the action of natural secretion, the inactivated virus naturally removes from the nasopharynx outward to the nose or inward to the stomach.

The nasal spray works by generating a physical barrier that stops the virus from taking grip of the surface in the nasopharynx. This barrier mechanism has been shown through in vitro testing performed by a reputable BSL-3 laboratory situated in WY. The use of the nasal spray is mainly effective since it targets the nasopharynx which has been recognized as the main entry point for the virus.

The inimitable technology of COVIXYL-V is filed to international PCT patent (PT/US20/55772).

ELAH has been widely studied in toxicity, metabolism, and effectiveness in vitro and in vivo. These studies confirmed that it has no metabolic, pharmacological, or immunologic action against the human body.

This product has been submitted to the FDA for Pre-Emergency Use Authorization and is pending approval for commercial use in the U.S.


[2] Nasitrol (Amcyte Pharma)

Company: Amcyte Pharma

Active Compound: iota carrageenan, a sulfated polysaccharide synthesized by red algae.

Mechanism of action:

The nasal cavity and the rhino-pharynx are the main sites of the initial replication of SARS-CoV-2. Its active constituent, iota-carrageenan, has anti-viral activity through its interaction with the viral surface, stopping viral entry and capturing viral particles released by infected cells. The spray is formulated to decrease the viral load in upper respiratory airways and prevent viruses from proliferating and spreading into the lungs.

Clinical Trials:

Research studies at the University of Tennessee Health Science Center have shown that the formulation inhibits infection by SARS-CoV-2, the virus that causes COVID-19, in vitro.

The research study (NCT04590365), was conducted at eight hospital ICUs in 394 clinically healthy physicians, nurses, and other medical professionals who provided care to COVID-19 patients and who had not yet been vaccinated. The participants were randomly allocated to receive four daily doses of Nasitrol spray or placebo for 21 days. The primary endpoint was clinical COVID-19 infection, as confirmed by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing, over 21 days. The occurrence of COVID-19 infection was significantly lower in the Nasitrol group compared with placebo, one percent versus five percent, respectively. 

According to a study led by Dr. Juan Figueroa of The Cesar Milstein Research Institute in Argentina and Dr. Mónica Lombardo of the CEMIC University Hospital in Buenos Aires, and sponsored by the Ministry of Science, Technology and Innovation of Argentina provide evidence that the simple intervention of a nasal spray with iota-carrageenan, in addition to hand hygiene, use of personal protective equipment and social distancing, could provide additional protection against transmission.


[3]IGM-6268

Company: IGM Biosciences,California,USA

Active Compound: The engineered IgMs antibodies which have a stronger ‘neutralizing’ effect against more than 20 variants of SARS-CoV-2

Mechanism of Action: engineered IgMs antibodies neutralize SARS-CoV-2

Clinical Trials:

As per a report in Nature, When IGM-628 squirted into the noses of mice either six hours before or six hours after infection, the engineered IgMs sharply reduced the amount of virus in the rodents’ lungs two days after infection.

Comments

An envisions these antibodies as a kind of chemical mask that could be used by anyone who has been exposed to SARS-CoV-2, and as an extra line of defense for people who might not be fully protected by vaccines. Because IgM molecules are relatively stable, it might be feasible to formulate them into a nasal spray to be bought at a pharmacy and kept for emergency use.


[4]Carragelose

Company: Marinomed Biotech

Active Compound: Carragelose® is a sulfated polymer from red seaweed and is a unique, broadly active antiviral compound.

Mode of Action:

Carragelose® forms a layer on the mucosa wrapping entering viruses, thereby inactivating them, and preventing them from infecting cells

Clinical Trials:

The company’s in vitro data on SARS-CoV-2 spike pseudotyped lentivirus and replication-competent SARS-CoV-2 recommend that administration of iota-carrageenan may be effective and safe prophylaxis or treatment for SARS-CoV-2 infections. Additionally, iota-carrageenan illustrates an equivalent effectivity against SARS-CoV-2 as a neutralizing antiserum and soluble ACE2 receptor. both well-accepted parameters for clinical performance. 

The company`s clinical data showed that treatment with iota-carrageenan either prophylactically or therapeutically may be similarly effective in humans suffering from COVID-19. Clinical data and post-market surveillance data showed that iota-carrageenan is well-tolerated and the number of reported adverse events is very low.

Comments:

Marinomed is having 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.


[5] Enovid (SaNOtize)

Company: Sanitize
Active Compound: Nitric Oxide
Mode of Action: Nitric oxide has inhibiting activity against SARS-CoV-2
Clinical Trials:

In a randomized, double-blind, placebo-controlled Phase 2 trial that assessed 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 decreased by more than 99%. The majority of these patients had been infected with the UK variant, which is considered a variant of concern.


[6] Povidone Iodine (PVP-I) Oro-Nasal Spray

Company/Research institute: Department of ENT & Head Neck Surgery, Dhaka Medical College & Hospital, Dhaka, Bangladesh
Active Compound: Povidone Iodine

Mode of Action:

PVP-I forms a protective layer or coating over nasal and oral mucosa so that SARS-CoV-2 can’t bind with the ACE-2 receptor and prevent their entry inside.

Clinical Trials:

PVP-I is a strong microbicidal (chemical) agent, having 99.99% virucidal efficacy in its only 0.23% concentration, irrespective of all known viruses, even in SARS-CoV-2 (in vitro) (Arefin et al.,2020).

As per clinical trial of ‘’ Virucidal efficacy of PVP-I on SARS- CoV-2 in the nasopharynx (NCT04549376), Researchers proposing 0.6% PVP-I Oro-Nasal spray is to be used as protective measures. In clinical trials, among 189 patients 0.6% PVP-I nasal spray showed better efficacy (, i.e., about 81.5%) than other (0.4%, 0.5% PVP-I nasal spray) with almost no mucosal irritation.

Comments:

Though it is proved and established that long-term (1–2 months) application of this minimum amount of PVP-I is quite safe But researchers recommend after continuous use of 1–2-week 1-day interval (weekly holiday) should be given. Effective virucidal agent against all coronaviruses, including SARS- COV-2.  Effective in case of both pre and post-exposure. 

Effective for healthy individuals (for protection) as well as COVID-19 patients also (for reduction of viral load and SARS-CoV-2 transmissibility for close contacts/ family members).  Almost no side effects (mucosal irritation, thyroid dysfunction, teeth staining,).

•This minimum concentration of PVP-I (0.6%) has the least possibility of doing any harm to the human body (nasal or oral mucosa). More concentration is being used on the eye, ear, mucosa of the oral cavity, oropharynx since before. Reduces disease burden by minimizing sign- symptoms, like nasal congestion, sore throat


[7]Foralumab

Company: British biotech Tiziana Life Sciences 
Active Compound: Fully human anti-CD3 monoclonal antibody (mAb),

Mode of Action:

Nasal administration with Foralumab could potentially modulate or stimulate the immune system to suppress cytokine storm and reduce respiratory failure inCOVID-19 patients 

Clinical Trials:

Nasal administration of Foralumab is a potentially transformative immunomodulatory method for treating patients with a variety of human diseases. 

Results from animal studies have shown that nasal administration of anti-CD3 induces regulatory T cells that suppress inflammation and ameliorate diseases in animal models. This scientific progression delivers the basis to move forward with the clinical development of nasally administered Foralumab in COVID-19 disease.

Comments:

Tiziana has a globally exclusive license for nasal administration of Foralumab and other anti-CD3 mAbs for the treatment of neurodegenerative and other diseases. 

The Company before proclaimed development of a robust formulation and delivery of Foralumab using a nasal spray device and the successful completion of a Phase 1 trial showing that the treatment was well-tolerated and showed positive immunomodulatory effects as measured by biomarker analysis (https://www.tizianalifesciences.com/news-item?s=2018-11-28-tiziana-announces-initiation-of-phase-1-clinical-trial-with-nasal-administration-of-foralumab-a-fully-human-anti-cluster-definition-3-monoclonal-antibody-anti-cd3-mab-in-healthy-volunteers

The company`s proprietary immunotherapeutic approach using nasal, inhalation, and oral administration of mAbs are novel and promising therapies that stimulate or modulate the immune system so that T regulatory cells are supercharged to prevent inflammation. The common underlying concept in these alternative delivery approaches is to support one’s own body defense to fight against inflammation in Covid-19.


[8] Xlear

Company/Research Institute: Utah State University and NorthwesternUniversity, USA.
Active Compound: grapefruit seed extract and xylitol 
Mode of Action:

The Grapefruit seed extract kills the virus, while the xylitol prevents the virus from attaching to the cell walls.

Clinical Research:

The imaging research study component was performed at the BioCryo facility of Northwestern University’s NUANCE Center. The study tested SARS-CoV-2 virus titers and LRV against a single concentration of Xlear nasal spray. According to the study, “After a 25-minute contact time, the nasal spray reduced virus from 4.2 to 1.7 log10 CCID50 per 0.1 mL, a statistically significant reduction (P<0.001) of 2.5 log10 CCID50.” The Northwestern/Utah State Study is the newest in a string of studies to reach the conclusion that Xlear is effective against the SARS-CoV-2.

Comments:

“Because there are no risk factors in using the X/GSE combination therapy, and [Xlear] nasal spray is over the counter available without a prescription, and [Xlear] allows for comfortable long-term mask-wearing, adoption of this preventive anti-viral therapy should be encouraged.”


[9]Taffix

Company: Nasus Pharma
Active Compound:

HPMC is a familiar and safe pharmaceutical compound identified to make a thin gel over mucosal surfaces and is widely used in artificial tears (Systain®) and as a nasal powder against allergic rhinitis. Nasus technology makes uniform small microspheres that generate an even thin gel over the nasal mucosa.

Mode of Action

Taffix is a powder nasal spray that upon reaching the nasal mucosa generates an active HPMC gel layer. Taffix also creates a low pH environment in the nasal cavity where viruses can no longer exist. The mechanical defense of the acidic gel prevents many viruses including SARS-CoV-2 from entering the nasal cells and reducing the risk of infection.

Clinical Research:
Comments:

According to the company, to protect against airborne viruses Taffix should be used prior to exposure to a risky environment where viruses may be airborne. Taffix can be applied 3 times a day.


[10]Bentrio (AM-301)

Company: Auris medical
Active Compound: bentonite
Mode of Action:

Bentrio is a nasal spray having a new triple mode of action that is intended to help protect against airborne infections, including COVID-19. Bentrio is a gel emulsion thixotropic property. After it has been sprayed into the nose, it converts into a gel again and forms the protective film on the nasal mucosa.

Viruses inhaled through the nose are attracted and trapped by electrostatic effects. The stuck viruses are then removed naturally from the nasal cavity through mucociliary clearance and removed via the digestive tract. Additionally, it moisturizes the nasal mucosa.

Clinical Research:

Prophylactic treatment with AM-301 is protective against SARS-CoV-2 infection. The daily application of the product starting 10 minutes before inoculation led to a 2-log (99%) reduction in viral titer by Day 4 compared to controls. Patients who received the product daily, starting 24 or 30 hours after viral infection, also had a lower viral titer, corresponding to a 12- or 14-fold lower TCID50 at the end of the treatment. The time profile of SARS-CoV-2 infection was significantly decelerated compared to controls both in the case of prophylactic treatment and in the case of mitigation treatment starting 24- or 30-hours post-infection.


[11]Baton Rouge General`s covid 19 spray

Company/Research Centre: Baton Rouge General Medical Centre
 Not much information


[12] Heparin Based Nasal Spray

Company/Research Institute: University of Melbourne, Australia
Active Compound: Heparin
Mode of Action:

Melbourne researchers grew nasal epithelial cells in the lab and added SARS-CoV-2 onto them and then inundated the media with heparin. They saw that the heparin presents in the media bound to the virus and prevent it from penetrating the cells. The heparin in the media delivers an alternative binding site to the heparin on the cells’ surface and keeps the virus away from the ACE2 receptors. The research team hypothesizes that spraying heparin in the nose could have a similar neutralizing effect.

Clinical Research:

In a study conducted by St Vincent’s Hospital in Melbourne, team gave a hefty dose of heparin to adults in ICU with acute respiratory distress syndrome through a ventilator. The study showed that heparin is not absorbed into the bloodstream when inhaled and reduces side-effects and avoids the hazard of bleeding that intravenous administration poses.


[13]GLS-1200 nasal spray

Company/Research Institute: GeneOne Life Science
Active Compound: quinine diluted in saline
Mode of Action: quinine stimulates nasal cells to secrete compounds that may prevent growth of bacteria and reduce viruses from reproducing.

Clinical Research:

As per company information, a clinical Phase II study will conduct. In this study, GLS-1200 will be self-administered as a spray to the nose, the main entry point for COVID-19 infection. GLS-1200 will act to stimulate nasal cells to produce nitric oxide (NO). NO has been shown to prevent SARS coronavirus growth and infectivity. This study of GLS-1200 will enroll a total of 225 participants into a randomized, double-blind, placebo-controlled clinical trial. The study will examine whether three-times daily nasal administration of GLS-1200 over 4 weeks can prevent infection with COVID-19 while in use.


[14] Azelastine nasal spray

Company/Research Institute: Central European Biotech Incubator and Accelerator
Active Compound: azelastine
Mode of Action: antihistamine azelastine has a potent anti-viral effect against SARS-CoV-2 and its variants in several in vitro assays.
Clinical Research:

The company conducted a double-blind, placebo-controlled Phase 2 clinical trial at the University of Cologne, Germany in 84 volunteers who were positive for SARS-CoV-2. Treatment with azelastine nasal spray reduced the SARS-CoV-2 viral load in the volunteers. A reduction in viral numbers of around 97% (up to around 30-fold) was seen in those treated with azelastine compared to the placebo (nasal spray buffer alone) after 1 week of treatment. 

Comments:

According to Eszter Nagy, MD Ph.D., CEO, CSO, and founder of CEBINA, azelastine as an approved drug used for allergy medication for 30 years and already on the market as a nasal spray, it could be immediately be introduced as a prophylactic or post-exposure anti-COVID solution as per clinical trial data.

[15] Chantix™ (varenicline) and simpinicline

Company/Research Institute: Oyster Point Pharma
Active Compound: Varenicline and Simpinicline
Mode of action: varenicline binds a stretch of 11 amino acids in the spike protein of SARS-CoV-2 which prevents the virus from binding the nACh receptors.

Clinical Research:

In studies on rhesus macaques, monkeys received snorts of varenicline before and after infection with an enormous dose of the virus. Researchers collected nasal swabs to test for virus on days 1, 2, 4, and 5, and then the animals were euthanized and their tissues observed. the nose swabs revealed an enormous reduction in viral genomes in corresponding to the treatments


[16] BMG0705 Nasal Spray

Company/Research Institute: BMG Pharma
Active Compound: Hydrogen Peroxide combined with Hyaluronic Acid.
Mode of Action:

Hydrogen Peroxide and Hyaluronic Acid combinedly create a protective barrier, adhering to the nasal mucosa which can stop COVID-19 and other infections and prevents them from deteriorating.

Clinical Research:

The clinical study related to spray enrolled a total of 106 people, who successfully completed an experimental protocol in 2021. The results from the analysis showed that the active intervention under investigation can be effective in increasing the negativity rate of a positive PCR nose swab test for SARS-CoV-2. 


[17]Viraleze

Company/Research institute:Starpharma,Australia
Active compound: -----
Mode of Action: -----
Clinical Research:

Viraleze administered nasally reduced viral load by more than 99.9% in the lungs and trachea of animals.

The research study conducted at The Scripps Research Institute used a humanized SARS-CoV-2 mouse model suggested by the WHO. The results demonstrate that Viraleze administered nasally significantly reduced SARS-CoV-2 viral load in the respiratory tract, in the blood, and in other organs inViraleze treated animals.

[18] University of Birmingham anti-covid 19 nasal sprays

Company/Research institute: University of Birmingham
Active Compound: Spray is composed of two polysaccharide polymers. Carrageenan is commonly used in foods as a thickening agent andgellan which was selected for its ability to stick to cells inside the nose.
Mode of Action:

The spray works in two ways. Firstly, it catches and coats the virus inside the nose, from where it can be removed via the usual routes either by nose-blowing or swallowing. Then, since the virus is encapsulated in the spray’s viscous coating, it is prevented from being uptaken by the body. That means it will decrease the viral load in the body, but also even if virus particles are passed on to another person through a sneeze or cough, that person is less likely to be infected by active virus particles.

Clinical Research:

A pre-print study (not yet peer-reviewed) defines cell culture that tested the ability of the formulation to inhibit COVID-19 infection. These studies presented the product can deliver significant (minimum of p<0.05) suppression of infection in cell cultures challenged by live virus compared to untreated controls, an effect was seen up to 48 hours and when diluted many times. 

[19]BioBlock Covid-19 Nasal Spray Containing Anti SARS-CoV-2 Antibodies

Company/ Research Institute:Scientists in Estonia
Active Compound: polyclonal antibodies derived from the colostrum of immunized cows.
Mode of Action:

The nasal spray is made up of polyclonal antibodies derived from the colostrum of immunized cows. The antibodies exhibit high efficiency in inhibiting the interaction between SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2 (ACE2). A nasal spray formulation with colostrum antibodies persists in the human nasal mucosa for at least 4 hours.

Clinical Research:

Scientists enrolled 16 healthy volunteers for studies. The antibody preparation was administered at two different concentrations via nasal spray twice into each nostril. The nasal samples were collected 1 and 4 hours after administration of the antibody preparation to measure antibody levels in the nasal cavity. The findings revealed that high amounts of anti-SARS-CoV-2 antibodies could be detected in the nasal mucosa even after 4 hours of spraying.

Comments:

To induce antibody production, the scientists immunized 8 cows with SARS-CoV-2 spike receptor-binding domain (RBD) protein in proper adjuvant solutions twice at an interval of 3 weeks. Afterward, they administered the cows with one booster dose of SARS-CoV-2 trimeric spike protein two weeks after the 2nd vaccine dose.

In mammals, antibodies developed against exogenous pathogens are naturally accumulated in the colostrum so that the protective immunity can be transferred to newborns through the colostrum. Given this natural phenomenon, the scientists collected colostrum from each immunized cow as an enriched source of anti-SARS-CoV-2 polyclonal antibodies.

[20] MIR-19

Company/Research institute: Russian Institute of Immunology
Active Compound: small interfering RNA
Mode of Action:

Small interfering RNA specific to the SARS-CoV-2 genome is highly effective at ‘turning off’ the copying (replication) of the virus and preventing the most severe forms of coronavirus infection.

Clinical Research:

MIR-19 has so far completed Phase I clinical trials on hamsters. The hamsters were infected with coronavirus and developed a slight cough as a result. And after the administration of Spray MIR-19, the degree of coughing goes down.MIR-19 is currently being studied in Phase II clinical trials - on human Covid-19 patients.


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