ADDovenom: Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming

Archive ouverte

Menzies, Stefanie | Arinto-Garcia, Raquel | Amorim, Fernanda Gobbi | Cardoso, Iara Aimê | Abada, Camille | Crasset, Thomas | Durbesson, Fabien | Edge, Rebecca | El-Kazzi, Priscila | Hall, Sophie | Redureau, Damien | Stenner, Richard | Boldrini-França, Johara | Sun, Huan | Roldão, António | Alves, Paula | Harrison, Robert | Vincentelli, Renaud | Berger, Imre | Quinton, Loïc | Casewell, Nicholas | Schaffitzel, Christiane

Edité par CCSD ; MDPI -

International audience. Snakebite envenoming can be a life-threatening medical emergency that requires prompt medical intervention to neutralise the effects of venom toxins. Each year up to 138,000 people die from snakebites and threefold more victims suffer life-altering disabilities. The current treatment of snakebite relies solely on antivenom—polyclonal antibodies isolated from the plasma of hyperimmunised animals—which is associated with numerous deficiencies. The ADDovenom project seeks to deliver a novel snakebite therapy, through the use of an innovative protein-based scaffold as a next-generation antivenom. The ADDomer is a megadalton-sized, thermostable synthetic nanoparticle derived from the adenovirus penton base protein; it has 60 high-avidity binding sites to neutralise venom toxins. Here, we outline our experimental strategies to achieve this goal using state-of-the-art protein engineering, expression technology and mass spectrometry, as well as in vitro and in vivo venom neutralisation assays. We anticipate that the approaches described here will produce antivenom with unparalleled efficacy, safety and affordability.

Suggestions

Du même auteur

In vitro generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2

Archive ouverte | Buzas, Dora | CCSD

International audience. Abstract Background Due to COVID-19, pandemic preparedness emerges as a key imperative, necessitating new approaches to accelerate development of reagents against infectious pathogens. Method...

The free fatty acid–binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron

Archive ouverte | Toelzer, Christine | CCSD

International audience. As coronavirus disease 2019 (COVID-19) persists, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations....

The Free Fatty Acid-Binding Pocket is a Conserved Hallmark in Pathogenic β-Coronavirus Spike Proteins from SARS-CoV to Omicron

Archive ouverte | Toelzer, Christine | CCSD

Abstract As COVID-19 persists, severe acquired respiratory syndrome coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor-binding domain (RBD) comprises a free fatt...

Chargement des enrichissements...