Rediocides A and G as Potential Antitoxins Against Cobra Venom

• Published in: Chemistry & biodiversity 2009-09, Vol.6 (9), p.1404-1414
• Main Authors: Utsintong, Maleeruk, Kaewnoi, Atchara, Leelamanit, Wichet, Olson, Arthur J., Vajragupta, Opa
• Format: Article
• Language: English
• Subjects: Animals; Antitoxins; Antitoxins - chemistry; Antitoxins - pharmacology; Antivenoms; Binding Sites; Cobra Neurotoxin Proteins - chemistry; Cobra Neurotoxin Proteins - metabolism; Computer Simulation; Detoxification; Diterpenes - chemistry; Diterpenes - pharmacology; Hydrogen Bonding; Macrolides - chemistry; Macrolides - pharmacology; Mice; Naja kaouthia; Protein Binding; Receptors, Nicotinic - chemistry; Receptors, Nicotinic - metabolism; Rediocides A and G; Trigonostemon reidioides; α-Cobratoxin
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.200800204

Rediocides A and G, the principle components of Trigonostemon reidioides (Kurz) Craib, which is known as Lotthanong in Thai, were investigated for a detoxification mechanism against Naja kaouthia venom by in silico, in vitro, and in vivo methods. Molecular dockings of α‐cobratoxin with rediocides A and G were performed, and the binding energies were found to be −14.17 and −14.14 kcal/mol, respectively. Rediocides bind to α‐cobratoxin at the same location as α‐cobratoxin binds to the nicotinic acetylcholine receptor (nAChR), i.e., at the Asp27, Phe29, Arg33, Gly34, Lys35, and Val37 residues. α‐Cobratoxin cannot bind to nAChR, because some of its binding sites are occupied with rediocides. From in vitro SDS‐PAGE, it was found that rediocides can diminish the bands of α‐cobratoxin. In the presence of acetylcholine‐binding protein (AChBP), it was apparent that rediocides can bind both α‐cobratoxin and AChBP. From an in vivo test, it was found that injection of rediocides at 0.5 mg/kg immediately after an α‐cobratoxin dose of three times LD50 cannot prolong the survival time of mice. However, rediocide can prolong the survival time, if it is injected 30 min before the injection of α‐cobratoxin. The in vitro SDS‐PAGE and the in vivo results support the in silico detoxification mechanism of rediocides against cobra venom at a molecular level.