Snakebite-induced local tissue damage remains a challenge in snakebite envenoming management because venom toxins rapidly disrupt vascular and extracellular matrix integrity at the bite site. This study evaluated the inhibitory effect of marimastat, an inhibitor of zinc-dependent metalloproteinases, against local tissue damage induced by Indonesian Trimeresurus insularis and Calloselasma rhodostoma venoms in a mouse skin model. The minimum hemorrhagic dose (MHD) of C. rhodostoma venom was determined in BALB/c mice and estimated to be 7.07 µg, while the MHD of T. insularis was adopted from a previous study. Mice received intradermal injections of venom at 2× MHD, either alone or pre-incubated with marimastat at venom:marimastat ratios of 1:1, 1:5, and 1:10 based on MHD equivalents. Macroscopic hemorrhage and histopathological changes, including erythrocyte extravasation, inflammatory cell infiltration, and collagen degradation, were assessed three hours after injection. Both venoms induced marked hemorrhagic lesions and tissue damage. Marimastat reduced venom-induced hemorrhage in both models, with near-complete inhibition in the T. insularis 1:10 group and complete inhibition in the C. rhodostoma 1:10 group. Marimastat also decreased erythrocyte extravasation, inflammatory infiltration, and collagen degradation, indicating preservation of microvascular and dermal matrix integrity. These findings support the central role of snake venom metalloproteinases in local viperid tissue damage and highlight marimastat as a promising adjunctive treatment for reducing venom-induced skin injury.
Banana Lectin (BanLec) is a mannose-binding jacalin-related lectin that has attracted considerable scientific interest due to its affinity toward high-mannose-type N-glycans and its immunomodulatory and antiviral properties. It also has the potential to suppress cancer cell proliferation and stimulate macrophage activity. In this study, evolutionary relationships among BanLec sequences across the Musa genus were also examined, while the primary focus was the identification and characterization of BanLec-encoding genes from Musa acuminata subsp. malaccensis (Malaysian Dwarf Banana) and Musa balbisiana (Banana Klutuk Wulung), with emphasis on their molecular properties and potential interactions with a hypermannosylated N-glycan structure (Man8GlcNAc2) reported to be abundant in breast cancer. Seven and four high-confidence BanLec protein sequences were identified from M. acuminata subsp. malaccensis and M. balbisiana genomes, respectively, which all share conserved structural domains characteristic of BanLec with variable exon-intron organizations. Gene locations, duplications, and synteny analyses revealed lineage-specific diversification of lectin genes within each species and between the two Musa genomes. The identified BanLec proteins were modelled and then evaluated by molecular docking and molecular dynamics simulations using a hypermannosylated N-glycan structure. The computational binding analyses demonstrate that BanLec variants from different Musa genomes exhibit distinct energetic and structural preferences toward the hypermannosylated N-glycan structure. Among the tested complexes, Ma09_t10450 (M. acuminata subsp. malaccensis) showed the most stable interaction, followed by Mba09_g09930 (M. balbisiana), each demonstrating strongly favourable binding free energies (ΔG ≤ -22.43 ± 3.01 kcal mol⁻¹ and ΔG ≤ -17.87 ± 10.81 kcal mol⁻¹ respectively) and therefore considered suitable candidates for lectin binding assays conducted at neutral pH, 300 K, and physiological ionic strength. These findings strengthen BanLec's potential as a promising candidate for lectin-based biomarker development and glycan-targeted therapeutic applications.