Key result
Beta-cardiotoxin from king cobra venom acts as a natural beta-blocker targeting beta-1 and beta-2 receptors.
Beta-cardiotoxin is the first reported natural exogenous beta-blocker, discovered from king cobra venom, which decreases heart rate by targeting beta1 and beta2 adrenergic receptors.
May inspire venom-derived beta-blocker leads; leaves open translation from animal data to human therapy.
Snake venoms have provided a number of novel ligands with therapeutic potential. We have constructed a partial cDNA library from the mRNA of Ophiophagus hannah (king cobra) venom gland tissue and identified five new genes encoding proteins belonging to the three-finger toxin family of snake venom proteins. We have isolated and characterized one of these beta-sheet containing proteins with a mass of 7012.43 +/- 0.91 Da from the venom. The protein was nonlethal up to a dose of 10 mg/kg when injected intraperitoneally into Swiss albino mice. However, it induces labored breathing and death at a dose of 100 mg/kg. It does not show any hemolytic or anticoagulant activity. It caused a dose-dependent decrease of heart rate in vivo (anesthetized Sprague-Dawley rats) and also ex vivo (Langendorff isolated rat heart). This is in contrast to classical cardiotoxins from snake venom that increase the heart rate in animals. Radioligand displacement studies showed that this protein targets beta-adrenergic receptors with a binding affinity (Ki) of 5.3 and 2.3 microM toward beta1 and beta2 subtypes, respectively, to bring about its effect, and hence, it was named as beta-cardiotoxin. This is the first report of a natural exogenous beta-blocker.
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Rajagopalan et al. (2007) studied this question. beta-cardiotoxin was evaluated on heart rate and beta-adrenergic receptor binding affinity. Beta-cardiotoxin, a novel protein isolated from king cobra venom, acts as a natural exogenous beta-blocker by targeting beta-1 and beta-2 adrenergic receptors (Ki 5.3 and 2.3 microM, respectively).
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