Cone snails of the genus Conus have evolved to produce structurally distinct and functionally diverse venom peptides for defensive and predatory purposes. This nature-devised delicacy enlightened drug discovery and for decades, the bioactive cone snail venom peptides, known as conotoxins, have been widely explored for their therapeutic potential, yet we know very little about them. With the augmentation of computational algorithms from the realms of bioinformatics and machine learning, in silico strategies have made substantial contributions to facilitate conotoxin studies although still with certain limitations. In this review, we made a bibliometric analysis of in silico conotoxin studies from 2004 to 2024 and then discussed in silico strategies to not only efficiently classify conotoxin superfamilies but also speed up drug discovery from conotoxins, reveal binding modes of known conotoxin-ion channel interactions at a microscopic level and relate the mechanisms of ion channel modulation to its underlying molecular structure. We summarized the current progress of studies in this field and gave an outlook on prospects.
Keywords: binding modes; drug discovery; in silico strategies; venom peptides.