Predatory cone snails (Conus) developed a sophisticated neuropharmacological mechanism to capture prey, escape against other predators, and deter competitors. Their venom’s remarkable specificity for various ion channels and receptors is an evolutionary feat attributable to the venom’s variety of peptide components (conotoxins). However, what caused conotoxin divergence remains unclear and may be related to the role of prey shift. Principal component analysis revealed clustering events within diet subgroups indicating peptide sequence similarity patterns based on the prey they subdue. Molecular analyses using multiple sequence alignment and structural element analysis were conducted to observe the events at the molecular level that caused the subgrouping. Three distinct subgroups were identified. Results showed homologous regions and conserved residues within diet subgroups but divergent between other groups. We specified that these structural elements caused subgrouping in alpha conotoxins that may play a role in function specificity. In each diet subgroup, amino acid character, length of intervening amino acids between cysteine residues, and polypeptide length influenced subgrouping. This study provides molecular insights into the role of prey shift, specifically diet preference, in conotoxin divergence.

The biological origin of COVID-19 is linked to three pathophysiological conditions: immunosuppression, viral infection, and inflammation. In the Philippines, nine alkaloids with potential antiviral and anti-inflammatory effects have been isolated from two plants, Uncaria perrottetii and Uncaria lanosa f. philippinensis, and their potential for COVID-19 therapy were investigated. Results showed that mitraphylline (L5) and uncarine B (L6) are two potential candidates as they exhibited the best binding energy score, lowest binding interaction energies, and lowest RMSD score. MMPBSA analysis indicated that complex binding energies of -128.295 ± 16.787 kJ/mol and -44.940 ± 10.918 for A2AR-5 and 3CL-6, suggesting that mitraphylline is a potential competitive antagonist in A2AR of caffeine, which is a known antagonist and inhibitor of the receptors, and uncarine B is a candidate inhibitor of 3CL protease.

On January 31, 2020, WHO declared the global outbreak of novel Coronavirus as a public health emergency of international concern. The biological origin of COVID-19 is caused by three primary pathophysiological conditions: immunosuppression, viral infection, and inflammation. In the Philippines, nine alkaloids with potential antiviral and anti-inflammatory effects have been isolated from two plants, Uncaria perrottetii and Uncaria lanosa f. philippinensis. The binding site of A2AR was proven to be pocket 0, which is similar to the literature. Two drug candidates showed the best result for molecular docking: mitraphylline and rauniticine-allo-oxindole A for A2AR and 3CLpro receptors. Mitraphylline candidate showed the lowest free energy scores and RMSD scores. This study is extended to other in silico tests to prove the impact of the alkaloid against COVID-19.

Conotoxins are fast-evolving and highly diverse small, structured peptides found in venoms of predatory marine gastropods of the genus Conus. They are diverse yet exhibit superior stability, potency, and selectivity for various target receptors and subtypes; hence, they were proven valuable probes for drug discovery studies and models for protein evolution. The data structure of conotoxin peptide sequences in each gene superfamily was analyzed. Feature extraction showed diet- and geographical region-specific gene superfamilies. Using fast-Fourier transform (FFT) and principal component analysis (PCA), data structures indicated patterns of sequence similarity in conopeptides isolated in the same diet type. Clusters based on diet are prominent in the PCA plots and dendrograms. PCA clustering, node grouping, and feature extraction suggest the increasing role of dietary preference, providing insights on the driving force that pushed conotoxins to diverge and diversify.

White Feces Syndrome (WFS) is a disease that causes serious problems in the shrimp aquaculture industry and is highly linked to two bacterial species, namely, Enterocytozoon hepatopenaei (EHP) and Gram-negative Vibrio species. Due to the emergence of new diseases in shrimps and their unclear etiology, such as WFS, there is a need for the development of new therapeutic strategies that can improve the immunity of shrimps. Thus, in this study, we determined glycosidic compounds which can serve as immunostimulants that have high affinity towards P. monodon shrimp TLR9 to induce the NF-κB signaling pathway and strengthen shrimp immunity against viral and bacterial diseases. The glycosidic compounds were obtained from the Immulina polysaccharide. The protein structure was acquired through homology modeling using mouse TLR3 (SMTL ID: 7c77.1) as a template using the SWISS-MODEL webserver. Based on the docking studies, N-acetyl-glucosamine (ca. -6.99 kcal/mol), 2,3-methylfucose (ca. -6.78 kcal/mol), and 2-methyl glycose (ca. -6.66 kcal/mol) were the top-scoring compounds which have high binding affinity towards the target protein. By visualizing the ligand-protein interactions, we learned that ASN512 was the common binding residue among most of the top-scoring compounds and plays a crucial role in ligand-protein binding. Based on the MD studies, all compounds showed low RMSD values, except N-acetyl-glucosamine, indicating good ligand binding to the target protein. In the MMPBSA studies, we found that 2,3-methylfucose had the lowest average binding energy (ca. -41.507 ± 88.52); hence, this glycosidic compound shows the highest affinity towards shrimp TLR9. To conclude, all three top-scoring compounds have highly favorable agonistic binding towards P. monodon TLR9 given their low average binding energy values. To further affirm our conclusions, we recommend the use of in vivo and in vitro tests, as well as longer MD studies for more accurate simulations.