| Summary: | Within the Conidae family, the piscivorous <i>Conus</i> species have been a hotspot target for drug discovery. Here, we assess the relevance of <i>Conus</i> and their other feeding habits, and thus under distinctive evolutionary constraints, to highlight the potential of neglected molluscivorous and vermivorous species in biomedical research and pharmaceutical industry. By singling out the areas with inadequate <i>Conus</i> disquisition, such as the Tamil Nadu Coast and the Andaman Islands, research resources can be expanded and better protected through awareness. In this study, 728 <i>Conus</i> species and 190 species from three other genera (1 from <i>Californiconus</i>, 159 from <i>Conasprella</i> and 30 from <i>Profundiconus</i>) in the Conidae family are assessed. The phylogenetic relationships of the Conidae species are determined and their known feeding habits superimposed. The worm-hunting species appeared first, and later the mollusc- and fish-hunting species were derived independently in the Neogene period (around 23 million years ago). Interestingly, many <i>Conus</i> species in the warm and shallow waters become polyphagous, allowing them to hunt both fish and worms, given the opportunities. Such newly gained trait is multi originated. This is controversial, given the traditional idea that most <i>Conus</i> species are specialized to hunt certain prey categories. However, it shows the functional complexity and great potential of conopeptides from some worm-eating species. Pharmaceutical attempts and relevant omics data have been differentially obtained. Indeed, data from the fish-hunting species receive strong preference over the worm-hunting ones. Expectedly, conopeptides from the fish-hunting species are believed to include the most potential candidates for biomedical research. Our work revisits major findings throughout the <i>Conus</i> evolution and emphasizes the importance of increasing omics surveys complemented with further behavior observation studies. Hence, we claim that <i>Conus</i> species and their feeding habits are equally important, highlighting many places left for <i>Conus</i> exploration worldwide. We also discuss the Conotoxin drug discovery potentials and the urgency of protecting the bioresources of <i>Conus</i> species. In particular, some vermivorous species have demonstrated great potential in malaria therapy, while other conotoxins from several worm- and mollusc-eating species exhibited explicit correlation with SARS-CoV-2. Reclaiming idle data with new perspectives could also promote interdisciplinary studies in both virological and toxicological fields.
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