Biology subjects

Medaglia, C.

Publications and source records attributed to Medaglia, C..

5 recordsLinked to original sources

bioRxiv2024

Development of Broad-spectrum β-cyclodextrins-Based Nanomaterials Against Influenza Viruses

In recent decades, epidemics and pandemics have multiplied throughout the world, with viruses generally being the primary agents responsible. Among these, influenza viruses play a key role, as they cause severe respiratory distress, representing a major threat to public health. To enhance the response to viral disease outbreaks, there is a need for ready-to-use broad-spectrum antivirals. We have engineered macromolecules (named CD-SA) consisting of a {beta}-cyclodextrin (CD) scaffold modified with hydrophobic linkers in the primary face, onto which unitary sialic acid (SA) epitopes are covalently grafted, this to mimic influenza virus host receptors. In this study, we demonstrated that CD-SA, with a unitary SA, without extensive polysaccharides or specific connectivity, acts as a potent virucidal antiviral against several variants of human influenza type A and type B viruses. We also assessed the genetic barrier to resistance of CD-SA in vitro and successfully delayed emergence of resistance by combining CD-SA with interferon-{lambda}1 (IFN {lambda}1). Finally, we completed the characterization of the antiviral activity by conducting both ex vivo and in vivo studies, demonstrating a potent antiviral effect in human airway epithelia and in a mouse model of infection, higher than that of Oseltamivir, a currently approved anti-influenza antiviral.

microbiology↗

bioRxiv2022

Trapping virus-loaded aerosols using granular protein nanofibrils and iron oxyhydroxides nanoparticles

The ongoing COVID-19 pandemic has revealed that developing effective therapeutics against viruses might be outpaced by emerging variants,1-5 waning immunity,6-9 vaccine skepticism/hesitancy,10-12 lack of resources,13-16 and the time needed to develop virus-specific therapeutics,17,18 emphasizing the importance of non-pharmaceutical interventions as the first line of defense against virus outbreaks and pandemics.19-23 However, fighting the spread of airborne viruses has proven extremely challenging,23-28 much more if this needs to be achieved on a global scale and in an environmentally-friendly manner.29,30 Here, we introduce an aerosol filter made of granular material based on whey protein nanofibrils and iron oxyhydroxides nanoparticles. The material is environmentally-friendly, biodegradable, and composed mainly of a dairy industry byproduct.31 It features remarkable filtration efficiencies between 95.91% and 99.99% for both enveloped and non-enveloped viruses, including SARS-CoV-2, the influenza A virus strain H1N1, enterovirus 71, bacteriophage {Phi}6, and bacteriophage MS2. The developed material is safe to handle and recycle, with a simple baking step sufficient to inactivate trapped viruses. The high filtration efficiency, virtually-zero environmental impact, and low cost of the material illuminate a viable role in fighting current and future pandemics on a global scale.

microbiology↗

bioRxiv2021

A novel anti-influenza combined therapy assessed by single cell RNA-sequencing

Influenza makes millions of people ill every year, placing a large burden on the healthcare system and the economy. To develop a novel treatment against influenza, we combined virucidal sialylated cyclodextrins with interferon lambda and demonstrated, in human airway epithelia, that the two compounds inhibit the replication of a clinical H1N1 strain more efficiently when administered together rather than alone. We investigated the mechanism of action of the combined treatment by single cell RNA sequencing analysis and found that both the single and combined treatments impair viral replication to different extents across distinct epithelial cell types. We also showed that each cell type comprises multiple sub-types, whose proportions are altered by H1N1 infection, and assess the ability of the treatments to restore them. To the best of our knowledge this is the first study investigating the effectiveness of an antiviral therapy by transcriptomic studies at the single cell level.

genomics↗

bioRxiv2020

Methylene Blue has a potent antiviral activity against SARS-CoV-2 in the absence of UV-activation in vitro

Methylene blue is an FDA and EMA approved drug with an excellent safety profile. It displays broad-spectrum virucidal activity in the presence of UV light and has been shown to be effective in inactivating various viruses in blood products prior to transfusions. In addition, its use has been validated for methemoglobinemia and malaria treatment. Here we show the virucidal activity of methylene blue at low micromolar concentrations and in the absence of UV activation against SARS-CoV2.

microbiology↗

bioRxiv2020

Non-Toxic Virucidal Macromolecules Show High Efficacy Against Influenza Virus Ex Vivo and In Vivo

Influenza is one of the most widespread viral infections worldwide and represents a major public health problem. The risk that one of the next pandemics is caused by an influenza strain is very high. It is very important to develop broad-spectrum influenza antivirals to be ready for any possible vaccine shortcomings. Anti-influenza drugs are available but they are far from ideal. Arguably, an ideal antiviral should target conserved viral domains and be virucidal, i.e. irreversibly inhibit viral infectivity. Here, we describe a new class of broad-spectrum anti-influenza macromolecules that meets these criteria and displays exceedingly low toxicity. These compounds are based on a cyclodextrin core modified on its primary face with long hydrophobic linkers terminated in 6sialyl-N-acetyllactosamine (6SLN) or 3SLN. SLN enables nanomolar inhibition of the viruses while the hydrophobic linkers confer irreversibility to the inhibition. The combination of these two properties allows for efficacy in vitro against several human or avian influenza strains, as well as against a 2009 pandemic influenza strain ex vivo. Importantly, we show that, in mice, the compounds provide therapeutic efficacy when administered 24h post-infection allowing 90% survival as opposed to no survival for the placebo and oseltamivir..

microbiology↗