Throat spray formulated with virucidal pharmaceutical excipients as an effective early prophylactic or treatment strategy against pharyngitis post-exposure to SARS-CoV-2

SARS-CoV-2; the virus causing the Covid-19 pandemic; is transmitted by close contact and aerosol transmission routes. The major route of entry of SARS-CoV-2 is through the nose and mouth, and to some extent through the eyes. The throat (pharynx) is a common point of entry to the lungs from both the mouth and nose. In the case of eyes too, it is described that the virus travels through the lacrimal and nasolacrimal ducts (the tear ducts) and then into the nose, throat, trachea, and finally lung [28]. Thus, any virus accidentally entering through the mouth, nose, and/or eyes could be stopped/inactivated at the pharynx or nasopharynx with the use of a surfactant-based gargle or throat spray. SNEDDS are a proven method for poorly soluble substances work by increasing the solubility and bioavailability. SNEDDS are isotropic mixtures composed of oils, surfactants, and occasionally cosolvents. The ability of these formulations and methods to produce microemulsions or fine oil-in-water (o/w) emulsions after moderate stirring and dilution by water [32]. Entrapment of viruses by SNEDDS could be used as a mechanism of inactivation. A high residence time of the virus in the pharynx would further enhance this prophylactic effect. Throat sprays are widely used dosage form for throat infections and inflammation. Based on the convenience of using throat spray compared to throat paint, the former would be most suitable for prophylaxis [35].

We believe that using bioactives and surfactant therapy will prevent the attachment of the virus through its spike glycoproteins and provide good prevention of the incidence of viral infection. Encapsulation of bioactives in SNEDDS has been proven as a new method for enhancing their efficacy, stability, and utilization [32]. Nanoemulsions are a unique class of disinfectants produced by mixing a lipid-oil ‘discontinuous’ phase with an aqueous ‘continuous’ phase under high pressure. The result is an oil droplet of 200/600 nm in diameter that can fuse with and subsequently disrupt the membrane of a variety of different pathogens[18]. These lipid-containing preparations represent a new generation of disinfectants that disrupt selectively membranes of isolated prokaryotic cells and viruses but does not affect eukaryotic cells present in the tissue.

In-silico approach was used to find a natural bioactive and SNEDDS excipients that binds and prevents the attachment/internalization of SARS-CoV-2 is decisively a perfect therapeutic option in this period of constraint. One of these natural bioactives is CUR, which is a compound found in turmeric, a spice with known anti-inflammatory and antioxidant properties. In-silico analysis proved that CUR binds with spike protein with 6 hydrogen bonds with a score higher than nafamostat also it binds with angiotensin-converting enzyme 2 (ACE2) and the transmembrane protein serine protease 2 (TMPRSS2) with a score higher than hydroxychloroquine.

Pharyngitis, or inflammation of the pharynx (the back of the throat), can be a symptom of various respiratory infections, including those caused by viruses such as the SARS-CoV-2 virus, which is responsible for COVID-19. It's important to note that pharyngitis alone is not a specific or exclusive symptom of COVID-19, as it can occur in various respiratory infections and other conditions. There are currently no antiviral treatments designed specifically for sore throat, and existing products for sore throat have not been demonstrated to effectively address both inflammation and pain[11]. Orally administering anti-inflammatory drugs, such as paracetamol and ibuprofen, can alleviate pain. However, substantial doses and prolonged treatment periods are necessary to attain this effect, potentially leading to cellular toxicity and additional side effects [21], [22].

Herein, our aim in this study was to conduct a docking study to determine the potential interaction of certain bioactives, oils, co-surfactants, and surfactants with virus spike glycoprotein; and then using the bioactives and surfactants with identified virucidal activity to formulate a throat spray to be used as a prophylactic strategy to limit Pharyngitis induced in rats. This throat spray is envisioned to be useful for healthcare professionals who experience repeated exposure to infected patients.

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