BioAcyl Corp
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Moakes, R. J. A., Davies, S. P., Stamataki, Z., & Grover, L. M. (2020). Formulation of a composite nasal spray enabling enhanced surface coverage and prophylaxis of SARS-COV-2. bioRxiv, 2020.11.18.388645. Added by: Dr. Enrique Feoli (21/11/2020, 12:02) Last edited by: Dr. Enrique Feoli (01/12/2020, 11:17) |
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| Resource type: Journal Article BibTeX citation key: Moakes2020 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Inmunidad de mucosas Creators: Davies, Grover, Moakes, Stamataki Collection: bioRxiv |
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| Abstract |
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Airborne pathogens pose high risks in terms of both contraction and transmission within the respiratory pathways, in particular the nasal region. Although knowledge of airborne transmission has long been known, there is little in the way of adequate intervention that can protect the individual, or even prevent further spread. This study focuses on a nasal applicant with the capacity to combat such issues, by focussing on the SARS-CoV-2 virus. Formulation of a spray containing polysaccharides known for their mucoadhesive properties was undertaken and characterised for their mechanical, spray patterns and antiviral properties. The ability to engineer key behaviours such as yielding have been shown, through systematic understanding of a composite mixture containing two polymers: gellan and λcarrageenan. Furthermore, spray systems demonstrated highly potent antiviral capacities, resulting in complete inhibition of the virus when studied for both prophylaxis and prevention of spread. Finally, a mechanism has been proposed to explain such findings. Therefore, demonstrating the first fully preventative device, targeted to protect the lining of the upper respiratory pathways.
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| Notes |
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It is suggested that inhibition of the infection results through 3 main mechanisms: formation of a steric barrier at the cell interface, adsorption of the polymer to the virus, and/or physical entrapment of the virus in the sprayed layer. It is proposed that polymer adsorption is facilitated through charge-charge interactions at the cell and virus membrane. Although both anionic in nature, the contrast in virus inhibition infers that the carrageenan’s sulphate chemistry drives anchoring of the polymer to the substrate surface; likely through the formation of di-sulphide bridges with cationic membrane polysaccharides and/or proteins. The polymer thus provides a physical role, expanding the hydrodynamic volume around the cell/virus and preventing close proximity.[50] Even though the role that the negatively charged sulphate groups play in the ability to adsorb to the bio-interface, it is unclear from the data whether a link between the degree of sulphation and suppression of infection exists. Although not significant in the role of coating, gellan does demonstrate its applicability when considering prophylaxis through entrapment and elimination. The ability to engineer high viscosities and yielding behaviour at this point becomes key, proportionally slowing diffusivity, as described by the Stokes-Einstein relation.[51] To this end, diffusion of the virus towards the host cells can be hampered within timescales associated with typical nasal clearance.[52] In reality a combination of the 3 proposed mechanisms is likely to occur. To this end, physical entrapment is suggested to provide a first means of defence, simultaneously resulting in a secondary defence where cells and virus become coated. Thus, any virus particles having migrated to the cell interface are already inhibited to uptake. Likewise, the formation of new viruses as a result of shedding, become incapacitated. This combinatorial approach, coupled with the highly potent anti-viral capacity of the carrageenan towards SARS-CoV-2, provides a powerful spray device with the capacity to prevent both contraction and transmission. |