Bungarus multicinctus (many-banded krait) ranks among the world’s most medically significant venomous snakes. Its venom, predominantly composed of α-bungarotoxin neurotoxins in a complex mixture, induces life-threatening respiratory paralysis, pulmonary failure, and often multi-organ dysfunction following envenomation. Building upon our discovery that the chemical dye Cy7-SE attenuates the toxicity of Bungarus multicinctus venom, this study employed network pharmacology to analyze molecular docking parameters between Cy7-SE and α-bungarotoxin. We subsequently applied computational virtual screening to identify natural small molecules alleviating symptoms of B. multicinctus envenomation, followed by comprehensive in vitro and in vivo validation. Molecular docking revealed that Cy7-SE forms a stable complex with α-bungarotoxin through five hydrogen bonds, exhibiting a binding energy of -8. 49 kcal/mol. Using optimized GridBox parameters derived from this interaction, we performed batch molecular docking against the ZINC database, identifying 3, 118, 296 potential α-bungarotoxin-binding molecules. Through sequential filtering—binding energy ≤ -7 kcal/mol, ADMET prediction analysis, Lipinski’s rule screening, weighted refinement via Pandas library analysis, and final prioritization using PyMOL visualization—coupled with literature mining, the natural compound cyanidin-3-glucoside (C3G) was identified as a promising therapeutic candidate. Molecular dynamics simulations confirmed the stable binding of C3G to α-bungarotoxin. Surface plasmon resonance demonstrated that C3G and α-bungarotoxin have a strong binding affinity. In vivo studies showed that co-injection of high-dose C3G (300-fold molar equivalent to venom) with B. multicinctus venom significantly enhanced murine survival rates. Moreover, immediate post-envenomation administration of C3G at this dosage improved 24-hour survival and alleviated histopathological damage in diaphragmatic and pulmonary tissues. Notably, the protective effect of C3G relies on an extremely high molar excess and is mainly limited to co-administration or immediate post-envenomation intervention; this compound acts as a symptomatic ameliorating agent to delay disease progression and mitigate secondary tissue damage, rather than exerting direct or clinically significant venom neutralization, distinguishing it from antivenom.
Zhang Z, Jiang N, Xiao M, Hu S, Jia Q, Dong D, et al. (2026) Cyanidin-3-O-glucoside (C3G): A natural small-molecule compound for alleviating envenomation symptoms Induced by Bungarus multicinctus. PLoS Negl Trop Dis 20(4): e0014207. https://doi.org/10.1371/journal.pntd.0014207
