Rediocides A and G as potential antitoxins against cobra venom

Abstract

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 LD50cannot 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. © 2009 Verlag Helvetica Chimica Acta AG.