Developing self-assembling cyclodextrins to tackle the cytopathic activity of respiratory pathogens

Descripción del proyecto

Soluciones preventivas para las infecciones respiratorias

Los antivíricos que previenen infecciones respiratorias son esenciales para reducir la propagación y repercusión de las enfermedades víricas. La pandemia de COVID-19 constató la necesidad de este tipo de fármacos. En el proyecto CD-ResVir, financiado por las acciones Marie Skłodowska-Curie, se pretende desarrollar un novedoso sistema preventivo contra microorganismos patógenos respiratorios. La idea es crear matrices y funcionalizarlas con ligandos dirigidos a microorganismos patógenos para mejorar la afinidad y eficacia contra el coronavirus del síndrome respiratorio agudo grave de tipo 2 y otros virus respiratorios. Para crear las matrices, los investigadores se proponen emplear conjugados de ciclodextrinas: oligosacáridos cíclicos compuestos de unidades de glucosa. El objetivo a largo plazo es desarrollar un aerosol nasal de uso preventivo generalizado contra las infecciones respiratorias.

Objetivo

The covid-19 pandemic has arisen awareness about the importance of developing tools to fight viral infection. However, there is still a lack of products to be used by the public as preventive systems against respiratory pathogens. Different systems have been developed to target SARS-CoV-2 using its affinity for different ligands. However, a multivalent presentation of these ligands is necessary to overcome their low affinity, which often implies complex structures difficult to synthesise and characterise. CD-ResVir aims to overcome those challenges. Our group has a wide experience in the exploitation of cyclodextrin (CD) conjugates to create self-assembling systems. These can be functionalised with a ligand to target a pathogen, leading to a multivalent supramolecular scaffold. The great advantage of supramolecular assemblies over covalent strategies is their structural adaptability to the target, i.e. the assembly will adopt the most stable state, the one with maximal interactions. It is also very simple to mix self-assembling components to optimise the effect. In preliminary experiments, we have obtained robust data proving that a sialic acid-functionalised CD scaffold could offer protection to cells exposed to SARS-CoV-2, which has never been proved before with a supramolecular assembly. Here, we propose to optimise the system and go beyond, expanding the scope of respiratory infections that could be addressed, targeting different respiratory viruses and bacteria. The Chemical Biology processes behind this application will be studied, from the atomic level (interactions between CD and SARS-CoV-2 receptors) to the microscopic level, (templating effect of a virus for the self-assembly of our CD system). Pursuing a groundbreaking preventive nasal spray against respiratory infections, we have established a strategic partnership with an industrial collaborator. This will facilitate the transition of our research findings from the laboratory to the industrial setting.