Beta-Cardiotoxin: A novel protein isolated from the venom of Ophiophagus hannah (king cobra) showing beta-blocker activity

Abstract

Snake venoms have provided a number of novel ligands with therapeutic potential. We have constructed a cDNA library from the venom gland mRNA of Ophiophagus hannah (king cobra) and identified five novel proteins. We have isolated one of these proteins from the venom. This protein was non-lethal, non-hemolytic and has no anti-coagulant activity. It caused a decrease of heart rate in anesthetized rats and in isolated perfused heart. Radioligand displacement studies showed that this protein targets beta-adrenergic receptors with a Ki of 5.3 and 2.3 uM toward human beta1 and beta2 subtypes, respectively, and hence we named the protein as beta-cardiotoxin. This is the first report of an exogenous protein beta-blocker.