{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:20:27Z","timestamp":1783052427702,"version":"3.54.6"},"update-to":[{"DOI":"10.1371\/journal.pntd.0014207","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000}}],"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260386"],"award-info":[{"award-number":["82260386"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2025GXNSFDA069018"],"award-info":[{"award-number":["2025GXNSFDA069018"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Bungarus multicinctus (many-banded krait) ranks among the world\u2019s most medically significant venomous snakes. Its venom, predominantly composed of \u03b1-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\n                    <jats:italic>Bungarus multicinctus<\/jats:italic>\n                    venom, this study employed network pharmacology to analyze molecular docking parameters between Cy7-SE and \u03b1-bungarotoxin. We subsequently applied computational virtual screening to identify natural small molecules alleviating symptoms of\n                    <jats:italic>B. multicinctus<\/jats:italic>\n                    envenomation, followed by comprehensive in vitro and in vivo validation. Molecular docking revealed that Cy7-SE forms a stable complex with \u03b1-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 \u03b1-bungarotoxin-binding molecules. Through sequential filtering\u2014binding energy\u2009\u2264\u2009-7 kcal\/mol, ADMET prediction analysis, Lipinski\u2019s rule screening, weighted refinement via Pandas library analysis, and final prioritization using PyMOL visualization\u2014coupled 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 \u03b1-bungarotoxin. Surface plasmon resonance demonstrated that C3G and \u03b1-bungarotoxin have a strong binding affinity. In vivo studies showed that co-injection of high-dose C3G (300-fold molar equivalent to venom) with\n                    <jats:italic>B. multicinctus<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0014207","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:39:41Z","timestamp":1775583581000},"page":"e0014207","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cyanidin-3-O-glucoside (C3G): A natural small-molecule compound for alleviating envenomation symptoms Induced by Bungarus 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