Antiviral Activity of the Acyclic Nucleoside Phosphonate Prodrug LAVR-289 against Poxviruses and African Swine Fever Virus.

Poxviruses are double-stranded DNA viruses including relevant zoonotic pathogens with high morbidity and potential biological warfare threats. Although African swine fever virus belongs to the family and is not strictly classified as a member, both fall within the same class of that replicate in the cytoplasm. Among compounds targeting these viruses, acyclic nucleoside phosphonate (ANP) prodrugs are promising inhibitors of viral DNA polymerases.

A cancer immunoprofiling strategy using mass spectrometry coupled with bioorthogonal cleavage.

The accurate quantification of biomarkers is paramount in modern medicine, particularly in cancer where precise diagnosis is imperative for targeted therapy selection. In this paper we described a multiplexed analysis diagnostic approach based on cleavable MS-tagged antibodies. The technology uses MS-tag isotopologues and the sydnonimine-cyclooctyne click-and-release bioorthogonal reaction.

A Snake Toxin Derivative for Treatment of Hyponatremia and Polycystic Kidney Diseases.

Key Points: MQ232, a disulfide-bond reticulated peptide derived from a natural snake toxin, was optimized as a new aquaretic drug candidate. MQ232 showed very low acute and chronic toxicity in rat and a biodistribution in mice strongly in favor of the kidney organs. MQ232 induced a sole aquaretic effect and demonstrated high activities on hyponatremia and polycystic kidney disease models.

One-year post-exposure assessment of C-few-layer graphene biodistribution in mice: single repeated intratracheal administration.

Research on graphene-based nanomaterials has experienced exponential growth in the last few decades, driven by their unique properties and their future potential impact on our everyday life. With the increasing production and commercialization of these materials, there is significant interest in understanding their fate . Herein, we investigated the distribution of C-few-layer graphene (C-FLG) flakes (lat.

From a Cone Snail Toxin to a Competitive MC4R Antagonist.

The melanocortin 4 receptor (MC4R) plays a role in energy homeostasis and represents a target for treating energy balance disorders. For decades, synthetic ligands have been derived from MC4R endogenous agonists and antagonists, such as setmelanotide used to treat rare forms of genetic obesity. Recently, animal venoms have demonstrated their capacity to provide melanocortin ligands with toxins from a scorpion and a spider.

C910 chemical compound inhibits the traffiking of several bacterial AB toxins with cross-protection against influenza virus.

The development of anti-infectives against a large range of AB-like toxin-producing bacteria includes the identification of compounds disrupting toxin transport through both the endolysosomal and retrograde pathways. Here, we performed a high-throughput screening of compounds blocking Rac1 proteasomal degradation triggered by the Cytotoxic Necrotizing Factor-1 (CNF1) toxin, which was followed by orthogonal screens against two toxins that hijack the endolysosomal (diphtheria toxin) or retrograde (Shiga-like toxin 1) pathways to intoxicate cells. This led to the identification of the molecule C910 that induces the enlargement of EEA1-positive early endosomes associated with sorting defects of CNF1 and Shiga toxins to their trafficking pathways.

AAV-mediated gene therapy in Dystrophin-Dp71 deficient mouse leads to blood-retinal barrier restoration and oedema reabsorption.

Dystrophin-Dp71 being a key membrane cytoskeletal protein, expressed mainly in Müller cells that provide a mechanical link at the Müller cell membrane by direct binding to actin and a transmembrane protein complex. Its absence has been related to blood-retinal barrier (BRB) permeability through delocalization and down-regulation of the AQP4 and Kir4.1 channels (1).

Targeting channelrhodopsin-2 to ON-bipolar cells with vitreally administered AAV Restores ON and OFF visual responses in blind mice.

Most inherited retinal dystrophies display progressive photoreceptor cell degeneration leading to severe visual impairment. Optogenetic reactivation of retinal neurons mediated by adeno-associated virus (AAV) gene therapy has the potential to restore vision regardless of patient-specific mutations. The challenge for clinical translatability is to restore a vision as close to natural vision as possible, while using a surgically safe delivery route for the fragile degenerated retina.