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.
Antimicrobial resistance is a major public health issue raising growing concern in the face of dwindling response options. It is therefore urgent to find new anti-infective molecules enabling us to fight effectively against ever more numerous bacterial infections caused by ever more antibiotic-resistant bacteria. In this quest for new antibacterials, essential oils (or compounds extracted from essential oils) appear to be a promising therapeutic option. In the present work, we investigate the potential antibacterial synergy between a combination of terpinen-4-ol and α-terpineol (10:1) compared to standard tea tree oil. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined. Then, time kill assays, in vitro cytotoxicity and bactericidal activity on latent bacteria (persisters) were investigated. Finally, an in silico study of the pharmacokinetic parameters of α-terpineol was also performed. Altogether, our data demonstrate that the combination of terpinen-4-ol and α-terpineol might be a precious weapon to address ESKAPE pathogens.
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