Ensaio

Toxins affecting the cardiovascular system
The first venom-based drug captopril discovered in 1975 also formed the first oral angiotensin-converting enzyme
(ACE) inhibitor. This success story started with the observation of the toxic effect of venom from a Brazilian viper (Bothrops jararaca) that caused a sudden, massive drop in blood pressure. This piqued the interest of Nobel Prize winner Sir John Vane, who found that the viper venom was a potent inhibitor of ACE. Vane took this discovery to the pharmaceutical company Squibb where two scientists, David Cushman and Miguel Ondetti, created captopril, the first oral ACE inhibitor [18]. With the success of captopril, snake venoms have been explored for potential applications pertaining to the cardiovascular system. The binding of the anti-hypertensive drug captopril to its substrate ACE is shown in Figure 1c.
A toxin isolated from Indian cobra venom in the late
1940s was named cardiotoxin because it caused cardiac arrest when injected into experimental animals. Cardiotoxins, also known as cytotoxins are found exclusively in the venom of cobras and ringhals [19, 20], and are direct lytic factors and membrane-active polypeptides. They are single-chain, highly hydrophobic, basic, short polypeptides closely related to the α-neurotoxin that binds to nAChR, but cardiotoxins do not show any significant affinity for the receptors [21]. The main targets of cardiotoxins are on excitable cells. They cause depolarization and contracture of cardiac, skeletal and smooth muscles, and depolarization and loss of excitability of nerves.
Figure 1. (a) Structure of the α-cobratoxin-AChBP complex (1YI5) [from ref. 88]. (b) Nuclear magnetic resonance structure of an AChRpeptide (Torpedo californica, alpha subunit residues 182–202) in complex with α-bungarotoxin (1L4W) [from ref. 89]. (c) Complex of the anti-hypertensive drug captopril and the human testicular angiotensin I-converting enzyme (1UZF)