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Biology subjects

Gallet, S.

Publications and source records attributed to Gallet, S..

3 recordsLinked to original sources

Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels

COVID-19 is a complex disease with short- and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. Invasion of the brain by SARS-CoV-2 has been observed in humans and is postulated to be involved in post COVID condition. Brain infection is particularly pronounced in the K18-hACE2 mouse model of COVID-19. Here, we show that treatment of K18-hACE2 mice with melatonin and two melatonin-derived marketed drugs, agomelatine and ramelteon, prevent SARS-CoV-2 entry in the brain thereby reducing virus-induced damage of small cerebral vessels, immune cell infiltration and brain inflammation. Brain entry of SARS-CoV-2 through endothelial cells is prevented by melatonin through allosteric binding to human angiotensin-converting enzyme 2 (ACE2), which interferes with the cell entry receptor function of ACE2 for SARS-CoV-2. Our findings open new perspectives for the repurposing of melatonergic drugs in the prevention of brain infection by SARS-CoV-2 and COVID-19-related long-term neurological symptoms.

pharmacology and toxicology↗

Elicitation of potent SARS-CoV-2 neutralizing antibody responses through immunization using a versatile adenovirus-inspired multimerization platform

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown that vaccine preparedness is critical to anticipate a fast response to emergent pathogens with high infectivity. To rapidly reach herd immunity, an affordable, easy to store and versatile vaccine platform is thus desirable. We previously designed a non-infectious adenovirus-inspired nanoparticle (ADDomer), and in the present work, we efficiently decorated this original vaccine platform with glycosylated receptor binding domain (RBD) of SARS-CoV-2. Cryo-Electron Microscopy structure revealed that up to 60 copies of this antigenic domain were bound on a single ADDomer particle with the symmetrical arrangements of a dodecahedron. Mouse immunization with the RBD decorated particles showed as early as the first immunization a significant anti-coronavirus humoral response, which was boosted after a second immunization. Neutralization assays with spike pseudo-typed-virus demonstrated the elicitation of strong neutralization titers. Remarkably, the existence of pre-existing immunity against adenoviral-derived particles enhanced the humoral response against SARS-CoV-2. This plug and play vaccine platform revisits the way of using adenovirus to combat emergent pathogens while potentially taking advantage of the adenovirus pre-immunity.

microbiology↗

Responses of ground-dwelling spider assemblages to changes in vegetation from wet oligotrophic habitats of Western France

While many arthropod species are known to depend, directly or indirectly, on certain plant species or communities, it remains unclear to what extent vegetation shapes assemblages of other taxa, notably spiders. In this study, we tested whether the activity-density, composition, and diversity of ground-dwelling spiders were driven by changes in vegetation structure. Field sampling was conducted using pitfall traps in bogs, heathlands, and grasslands of Brittany (Western France) in 2013. A total of 8576 spider individuals were identified up to the species level (for a total of 141 species), as well as all plant species in more than 300 phytosociological releves. A generalised linear model showed that spider activity-density was negatively influenced by mean vegetation height and mean Ellenberg value for moisture. Indices of diversity (, {beta}, and functional diversities) increased with increasing vegetation height and shrub cover (GLMs). Variables driving spider composition were mean vegetation height, dwarf shrub cover, and low shrub cover (results from a redundancy analysis). Spiders, some of the most abundant arthropod predators, are thus strongly influenced by vegetation structure, including ground-dwelling species. Although later successional states are usually seen as detrimental to local biodiversity in Europe, our results suggest that allowing controlled development of the shrub layer could have a positive impact on the diversity of ground-dwelling spiders.

ecology↗