Biomedical Potential of the Neglected Molluscivorous and Vermivorous Conus Species

Abstract

Within the Conidae family, the piscivorous Conus species have been a hotspot target for drug discovery. Here, we assess the relevance of Conus 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 Conus 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 Conus species and 190 species from three other genera (1 from Californiconus, 159 from Conasprella and 30 from Profundiconus) 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 Conus 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 Conus 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 Conus evolution and emphasizes the importance of increasing omics surveys complemented with further behavior observation studies. Hence, we claim that Conus species and their feeding habits are equally important, highlighting many places left for Conus exploration worldwide. We also discuss the Conotoxin drug discovery potentials and the urgency of protecting the bioresources of Conus 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.

Keywords: Conus; biomedical compounds; distribution map; feeding habit; phylogenetic tree.

Figure 1

Phylogeny tree of 335 Conus species, constructed by using barcode sequences (12S, 16S and COI). Branch colors are set according to the feeding habit from Supplementary Table S1. Bootstrap values are presented by the numbers next to each branch. Species with feeding habits found have been assigned with branch colors accordingly. Names of species that have been involved in drug development are labeled in red.

Figure 2

The upper map shows the distribution of the monophagous and polyphagous Conus species clades from the phylogenetic tree (species listed in the Supplementary Table S2). Orange for molluscivous (M), red for piscivorous (P), green for vermivorous (V). Purple-color dots indicate the feeding habit of V+P (vermivorous and piscivorous); blue and black dots are for M+P (molluscivous and piscivorous); and the white dot is V+M (vermivorous and molluscivous). Conus species V+P are spread largely in the shallow waters of southeast Asia and Australia and African east coast, corresponding to the distribution areas of the most diversified Conus species. The distribution pattern of V+P species could result from a high competitive pressure and diversity of potential food sources in these areas. The lower map highlights the region where Conus species are most abundant and diversified, including the north coast of Australia and south and southeast Asia.

Figure 3

(A) Keyword cloud from the abstract of Conus studies over the past 20 years; (B) Statistics of current Conus studies. Ratio of six categories (genome assemblies, species under clinical trials, characterized protein structures, venom glands, species number and red list species) for Conus species of each feeding habit are presented in the radar plot. Orange for molluscivous (M), red for piscivorous (P), green for vermivorous (V) and species with insufficient data are presented in purple. Species with more than one feeding habit are counted separately in each group. Raw statistics can be seen in Supplementary Tables S3 and S4.