Anti-Inflammatory and Antiviral Osmotic Polymeric Film to Treat Covid-19 Early-Stage Infection

Abstract

Background: Covid-19 infection starts in the nasal cavity when viral S1 and RBD proteins bind to the host cell ACE2 receptors, the virus multiplies, causes cell lysis, and enters the circulation. This triggers a strong cytokine release and inflammation of the nasal mucosa. A multitarget approach of cleaning the nasal mucosa and suppressing chances of nasal and systemic inflammation should minimize severe respiratory consequences. Unfortunately, no such treatments are yet available. Methods: We describe the conception of an osmotic polymeric film using an in vitro nasal mucosa mimicking model, containing polymers to neutralize Covid-19 specific viral S1, RBD proteins and selected proinflammatory cytokines. Results: The filmogen barrier forms a stable and osmotic film on the nasal mucosa. Hypotonic liquid exudation from the nasal surface detaches and drains the inflammatory cytokines and other contaminants towards the film where selected polymers bind and neutralize SARS-CoV-2 spike S1 and RBD protein as well as Covid-19 disease-specific key pro-inflammatory IL-6, TNF-α, IL-10, IL-13, and GM-CSF cytokines. Conclusion:Minimizing the nasal surface concentration of pro-inflammatory cytokines and viruses should help nasal mucosa repair and avoid immune stress. This nearly instant, simple, scientific, safe, and logical approach should help attenuate Covid-19 induced systemic inflammation at an early stage without being affected by viral S1 spike protein mutations.

Conception and Clinical Efficacy of an Osmotic, Polymeric, Stable Nasal Filmogen Barrier for Preventive Treatment of Allergen and Pollution Induced Rhinitis and Respiratory Symptoms

“…Selection of osmotic filmogen ingredients: To find an ingredient which can be used to obtain a filmogen liquid for nasal application which is osmotic, non-cytotoxic, absorbent, and stable for 4-6h; multiple natural and synthetic ingredients were tested for osmotic and cytotoxic potential. The osmotic potential was quantified using multi-cellular live cell membrane dehydration model as described by Shrivastava et al (Ravi ) and cytotoxicity potential was measured as per the NF EN ISO 10993 (Évaluation biologique des dispositifs médicaux -Partie 5 : essais concernant la cytotoxicité in vitro n.d.) [26]. Cellular irritation potential was quantified using in vitro Bovine Corneal Opacity Test (BCOP) as described by Schrage et al [23].…”

“…The in vitro and in vivo cytotoxicity tests and 28-day, repeated dose, nasal application studies in rats showed no, local or systemic adverse effects. Exposing PCNS filmogen liquid on the in vitro NM mimicking multicellular live cell membrane showed that PCNS film is resistant to mechanical pressure, remains on NM for 4-6h, the osmotic activity continues during this period to attract and to trap free-floating NM contaminants towards PCNS film [26].…”

Polymeric Materials as Indispensable Tools to Fight RNA Viruses: SARS-CoV-2 and Influenza A

“…An in-between strategy of treatment and protection was the one followed by Shrivastava and co-workers. In their work, they described the conception of a long-lasting (4-6 h), absorbent, osmotic, glycerol-based polymeric film using an in vitro nasal mucosa-mimicking model, containing polymers capable of not only cleaning the nasal surface, but also neutralizing pro-inflammatory cytokines and the COVID-19 S protein (Covispray) [89]. Cytokines are responsible for the activation, regulation and amplification of the immune response and their production is usually highly regulated in order to prevent systemic damage [90].…”

“…Furthermore, at 5% concentration, the final Covispray composition neutralized nearly 30% of IL-6, 80% of TNF-α and GM-CSF, as well as more than 90% of IL-10 and IL-13 (pro-inflammatory cytokines responsible for nasal and systemic inflammation). Thus, the authors considered Covispray an effective, safe and preventive treatment against multiple nasal pathologies, including COVID-19 positive symptomatic patients in early stages of the disease [89]. In Table 1, there is a summary of the different polymer-based approaches described in different studies in order to avoid viral contaminations and diseases.…”

Clinical Efficacy of an Osmotic, Antiviral and Anti-Inflammatory Polymeric Nasal Film to Treat Covid-19 Early-Phase Respiratory Symptoms

“…The main site of Covid-19 virus mutation is S1 protein 32 The polymers incorporated in Covispray are selected to bind with whole COVID-19 S1 proteins as described in details by R Shrivastava et al 33 As viral mutations occur at the level of S1 protein, which may impact virus infectivity, antigenicity and immunogenic profile of the vaccines, 34 Covispray should be effective against all the covid-19 variants. 30 A Small Video attached with this article, explains the mode of action and the efficacy of Covispray.…”