The increasing prevalence of viral diseases represents a major threat to global human health, highlighting the urgent need for advanced tools to study viral infections, improve diagnostics, and develop effective antiviral therapies. Antibodies are central to the immune response against viruses and are widely used in research and diagnostics; however, their structural complexity and manufacturing process limit their areas of applications. Single‐domain antibodies—better known as nanobodies—derived from heavy chain‐only antibodies found in camelids have emerged as a promising alternative. Their unique characteristics—including small size, high stability, the capacity to access cryptic epitopes, and functionality within intracellular environments—make them particularly valuable for viral research. This review highlights recent developments of nanobodies for viral research, diagnostics, and therapeutic applications; discusses their key advantages and limitations; and briefly outlines the emerging role of artificial intelligence‐based technologies in facilitating their development to address the expanding burden of viral diseases.
AADC deficiency is a rare autosomal recessive disorder characterized by motor/neurodevelopmental symptoms. Approximately one‐third of patients experience recurrent hypoglycemia, with or without neurological involvement. To investigate whether specific variants identified in hypoglycemic patients underlie this metabolic phenotype, we characterized three amino‐terminal variants. The crystal structure of p.Asp15Gly revealed disruption of an inter‐subunit electrostatic network stabilizing the enzyme interface. Computational analyses predicted that p.Val33Leu and p.Gly36Arg perturb an essential catalytic element. Functional studies showed that p.Asp15Gly retained substantial catalytic activity and coenzyme affinity despite reduced stability, whereas p.Val33Leu and p.Gly36Arg exhibited increasing structural destabilization, reduced coenzyme affinity, and severe catalytic defects. These findings reveal distinct functional roles of the amino‐terminal‐domain, providing a molecular basis for the clinical variability of AADC deficiency.
Renal fibrosis is a hallmark of chronic kidney disease (CKD), but effective antifibrotic therapies are lacking. Pentraxin 3 (PTX3) is markedly upregulated in CKD patients and in a unilateral ureteral obstruction (UUO) model, correlating with renal injury, extracellular matrix accumulation, partial epithelial–mesenchymal transition markers, and TGF‐β1 signaling. Genetic deletion of Ptx3 significantly attenuates UUO‐induced fibrosis. Mechanistically, PTX3 promotes transcription of LTBP‐1 and fibronectin, facilitating latent TGF‐β1 activation and inducing a profibrotic partial EMT program in tubular epithelial cells without lineage conversion. Importantly, blockade of the PTX3/CD44 axis using a neutralizing αPTX3 antibody reduced serum creatinine levels and renal fibrosis, identifying PTX3 as a promising therapeutic target for CKD.
LigE is a periplasm‐targeted ATP‐dependent DNA ligase found in many Gram‐negative bacteria, including Neisseria gonorrhoeae . Although LigE has been shown to have a role in biofilm formation, many LigE‐possessing bacteria are also naturally competent, suggesting a possible role in transformation with extracellular DNA. Here, we demonstrate that LigE participates in competence by increasing transformation with nuclease‐damaged extracellular DNA that contains single‐stranded or cohesive breaks, and that this activity is dependent on its secretion signal peptide, indicating an extra‐cytoplasmic location of activity. We show that increased transformation with this restricted DNA is ATP‐dependent; however, the physiological source of ATP in the natural host remains unknown. Our findings highlight a potential role of Ngo‐LigE in Neisseria gonorrhoeae competence and horizontal gene transfer.
Progeria is an extremely rare genetic disease in which affected individuals age rapidly due to a specific mutation in the LMNA gene, which results in the production of progerin, an abnormal protein that damages cell nuclei and causes progressive multi‐organ disease. AIProSaB is an Italian association founded by Sammy Basso, who was diagnosed with progeria at the age of two, and by his parents. The association supports research, promotes experimental therapies, and provides information for families and clinicians, with a strong emphasis on understanding LMNA/progerin biology and developing targeted treatments and gene‐editing approaches. As part of our series on patient advocacy, FEBS Letters interviews Dr. Giovanna Lattanzi, a researcher at the CNR Institute of Molecular Genetics ‘Luigi Luca Cavalli‐Sforza’ in Bologna on the aims, achievements, and activities of AIProSaB.
