Inhibition of SARS-CoV-2 by a nasal spray based on bentonite

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiologic agent of COVID-19 (2019 coronavirus disease). To date, the COVID-19 pandemic has resulted in over 190 million confirmed SARS-CoV-2 infections and over 4 million COVID-related deaths.

This pandemic follows two previous global outbreaks of coronavirus, SARS in 2002-2003 and Middle East Respiratory Syndrome (MERS) in 2012. With new variants of SARS-CoV-2 emerging, the crisis poses an imminent threat despite vaccination programs and mitigation measures In progress. In addition, personal protection against infection needs to be improved.

SARS-CoV-2 infection is primarily acquired from airborne virions. The main site of infection in the human body is the nasopharyngeal epithelium, especially the hair cells. The epithelial lining of the nose is an essential gateway for viral infections. It is also an important site for viral replications.

Therefore, the nose is an important target for prophylaxis and also for therapy. In a recent study published on the bioRxiv* preprint server, Fabio Fais et al. has developed a safe and easy-to-use nasal spray, AM-301, a medical device marketed under the name Bentrio, to protect against infection with SARS-CoV-2 and potentially other viruses.

The researchers tested the safety and efficiency of AM-301 against SARS-CoV-2 and has been shown to be safe for the nasal epithelium. It also significantly reduced the viral titer in this study.

The mechanism of action of AM-301 is physical, i.e. the components are neither metabolized nor absorbed and therefore not pharmaceutical. As an added benefit, the researchers noted that the spray could be used against a wide range of viruses, allergens, and pollutants in the air.

Using a natural substance with broad pharmaceutical applications and virus-capturing properties such as clay, researchers have developed a simple and safe intervention to protect and improve nasal barrier function against SARS-CoV-2.

Bentonite

Bentonite is a clay mineral composed of thin sheets of aluminum silicate with a net negative charge. The team developed a nasal spray containing bentonite (magnesium aluminum silicate) in a matrix composed of mono-, di- and triglycerides, propylene glycol, xanthan gum, mannitol, disodium EDTA, citric acid and water.

Although bentonite has been known for many years to be able to capture viruses, this study represents its first application in capturing airborne viruses.

Formulation AM-301 is characterized as a white to light beige, odorless and tasteless aqueous gel emulsion with a pH of 6.0. “When we applied it to our own nasal lining or palmar skin, it had a soothing, non-irritating, lotion-like consistency,” the researchers explained in the article.

“Seeking to minimize potential side effects and facilitate frequent and consistent use, we have selected only inert ingredients such as pharmaceutical excipients and substances generally recognized as safe. “

MucilAir

Using a well-established model of primary human nasal epithelium, MucilAir, researchers demonstrated that AM-301 could: 1) prevent MucilAir from being infected with SARS-CoV-2, and 2) mitigate an established infection in MucilAir without any precedent. treatment.

AM-301 in alleviating SARS-CoV-2 infection. A, B Bar charts with average values ​​and individual data points. Test substances were applied 24 or 30 h after the start of the experiment (Protocols 1 and 2, respectively). C Linear mixed effects model. The log-linear scatter plot shows the logarithmically transformed data and concave curves for the negative control samples (untreated inserts, treated with saline and matrix solution; dashed curve) and for the inserts treated with AM-301 (curve continuous) (t = 3.68, p <0.01). The model shows a deceleration of exponential growth, as is generally observed for sigmoid behaviors.

Despite repeated applications for 4 days, AM-301 did not cause any adverse effects on MucilAir, except for a slight reduction in the frequency of eyelash fluttering. The researchers attributed this may be due to the viscosity of the preparation.

“The positive effects of AM-301 in reducing SARS-CoV-2 infection are corroborated by observations of mixed linear effects models, which showed significant decelerations in viral titer growth in prophylaxis and mitigation tests. “

In the initial stages of SARS-CoV-2 infection, the nasal passages are known to be infected with a high concentration of virus. As a result, the infected person is highly contagious and at risk of developing, by aspiration along the naso-oropharynx-lung axis, an infection of the lower respiratory tract. “The nasal microenvironment therefore plays a major role in the infection and clinical course of SARS-CoV-2”, the researchers observed.

In the nasal tract, two lines of protection are provided – a physical line, the epithelium of the nasal mucosa, and immune protection provided by immune cells residing in lymphoid tissue associated with the nasopharynx.

“Together, mucociliary clearance and immune responses should protect the nasal epithelium from pathogens, but infection can ensue with high viral exposure or dysfunction of these mucosal defenses.”

Despite the robust nasal barrier, viruses often manage to invade the body. Currently, no therapeutic solution is available. AM-301, as a non-pharmacological nasal spray, can be used to prevent infection with SARS-CoV-2 or to alleviate existing infection.

The encouraging results of this study call for further investigation in vivo and in humans to further evaluate AM-301 as a medical device with a broad spectrum of action against a battery of viruses, allergens and pollutants, the researchers write.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.