Spider-Venom Peptides: Structure, Bioactivity, Strategy, and Research Applications

Abstract

Spiders (Araneae), having thrived for over 300 million years, exhibit remarkable diversity, with 47,000 described species and an estimated 150,000 species in existence. Evolving with intricate venom, spiders are nature’s skilled predators. While only a small fraction of spiders pose a threat to humans, their venoms contain complex compounds, holding promise as drug leads. Spider venoms primarily serve to immobilize prey, achieved through neurotoxins targeting ion channels. Peptides constitute a major part of these venoms, displaying diverse pharmacological activities, and making them appealing for drug development. Moreover, spider-venom peptides have emerged as valuable tools for exploring human disease mechanisms. This review focuses on the roles of spider-venom peptides in spider survival strategies and their dual significance as pharmaceutical research tools. By integrating recent discoveries, it provides a comprehensive overview of these peptides, their targets, bioactivities, and their relevance in spider survival and medical research.

Identification and Evolutionary Analysis of the Widely Distributed CAP Superfamily in Spider Venom

“…The enzymes present in venom can cause cell damage, trigger the release of immune molecules, lead to inflammation, and, subsequently, induce pain and swelling in the prey [ 69 ]. On the other hand, neurotoxins act on various ion channels, disrupt neuronal function, and rapidly paralyze the prey [ 70 ]. Conserved enzymes and various neurotoxins work together to maintain the basic function of the venom, while also helping the spiders adapt to different ecology.…”

Zilucoplan: A Newly Approved Macrocyclic Peptide for Treatment of Anti-Acetylcholine Receptor Positive Myasthenia Gravis

“…Many peptides are obtained from natural sources [36], both terrestrial [37] and marine [38,39]. Chemical synthesis is also a remarkable source of peptides [40,41] and, in addition to classical solid-phase and solution-phase techniques [42], the introduction of sustainable and innovative processes was carried out for synthesis and purification methodologies [43,44].…”

Analgesic Peptides: From Natural Diversity to Rational Design

“…Spider venom contains a broad range of peptide toxins, exerting several activities in biological systems. To date, a large number of peptides with antinociceptive properties have been isolated from several spider venoms [40,41,52]. Typical spider peptides are rich in disulfide brides, which form the inhibitor cystine knot (ICK) motif.…”

“…Most contain six cysteine residues that form three disulfide bonds through connections between Cys 1 -Cys 4 , Cys 2 -Cys 5 and Cys 3 -Cys 6 . However, spider peptides may also contain four or even five disulfide bonds [52]. More peptides have shown antinociceptive effects by modulating ion channels such as acid-sensing ion channels (ASICs), stretch-activated channels (SACs), or voltage-gated ion channels, including calcium (Ca v ) and sodium (Na v ) channels.…”