Genomic and transcriptomic analyses reveal the adaptation to semi-aquatic and aquatic life in spiders

Posted by
  Genomic and transcriptomic analyses reveal the adaptation to semi-aquatic and aquatic life in spiders Abstract Spiders are largely terrestrial, but some lineages have independently adapted to marine and freshwater habitats. Although physiological and behavioral traits supporting these evolutionary transitions have been characterized, the genomic basis of adaptation to aquatic and semi-aquatic habitats in spiders remains unclear. Here, we report a chromosome-level genome assembly for the aquatic spider Argyroneta aquatica. Comparative analysis of 22 spider species supports two independent transitions in semi-aquatic (∼56 Mya) and aquatic (∼44 Mya) lineages. The aquatic spider show distinct respiratory morphology compared with terrestrial spiders, including anterior spiracles and denser tracheoles. Molecular evolution analyses identified lineage-specific shifts in selective constraint or evidence of positive selection linked to trachea development (e.g., Wnt-1, Catenin beta, TMEM23...

Unveiling new Kv1.3 channel blockers from scorpion venom: Characterization of Meuk7–3 and in silico design of its analogs for enhanced affinity and therapeutic potential

Posted by

 


Unveiling new Kv1.3 channel blockers from scorpion venom: Characterization of Meuk7–3 and in silico design of its analogs for enhanced affinity and therapeutic potential

Abstract

Kv1.3 channels are associated with autoimmune and neuroinflammatory diseases. Scorpion venom is an excellent source of inhibitors for Kv1.3. Kv1.3, a pivotal voltage-gated potassium channel, has emerged as a critical therapeutic target for combating autoimmune and neuroinflammatory diseases, including multiple sclerosis and rheumatoid arthritis. Some studies have tried to discover highly selective toxins targeting Kv1.3 channels, but it is still challenging. Here, we present a groundbreaking discovery of a potent peptide potassium channel blocker, Meuk7–3, derived from the venom of the scorpion, Mesobuthus crucittii. While similar to other Kv1.3 blockers, Meuk7–3's Lys19 residue may enhance its affinity for the channel. So, we redesigned the Meuk7–3 and generated three analogous, Meuk7–3 A, Meuk7–3B, and Meuk7–3C, to improve its drug-like properties and affinity to Kv1.3. Interaction evaluation with Kv1.3 revealed that Meuk7–3 and all its designed analogous could of Kv1.3's pore through the interaction of Lys19 of the peptide with Tyr447, Tyr797, Tyr1147, and Tyr1497, critical residues located at the channel pore of Kv1.3.However, the stability of the interaction of designed peptides with Kv1.3 was more than Meuk7–3. Binding affinity analysis revealed that all designed peptides had a better binding affinity to Kv1.3 than Meuk7–3. Among the three analogous, Meuk7–3 A was found to have better drug-like properties and interaction situations, including binding energy and affinity to Kv1.3, compared to Meuk-3 native. These findings provide new data for designing highly effective Kv1.3 inhibitors by computational tools for treating autoimmune and inflammatory diseases, although experimental testing is necessary to validate them.
Shariati, S., Mafakher, L., Shirani, M., & Baradaran, M. (2025). Unveiling new Kv1.3 channel blockers from scorpion venom: Characterization of Meuk7–3 and in silico design of its analogs for enhanced affinity and therapeutic potential. International Journal of Biological Macromolecules, 319, 145327. https://doi.org/10.1016/j.ijbiomac.2025.145327