In human history there has always been a close link between snakes and human perception of life and death. Their venoms have been used in many forms, from enhancement for weapons to medieval remedies. From ancient civilitation to the present snake venoms had been useful to créate new molecules, from the firts antivenom to captopril a new durgs. The searches were carried out during april of 2021. We performed the searches following the prisma methods and recomendations. Snake venoms are a mix of active substances such enzymes, proteins, and peptides. The therapeutic properties that are attributed to venoms can be grouped into the following pharmacological uses: first alterations of the cardiovascular system and nervous system; and other indications such as cancer treatment, antimicrobial therapy, and management of coagulation disorders. The therapeutic potential of Colombian snake venoms is immense, and they can help generate new treatments for multiple pathologies. Using “omics” technologies will allow identifying more potential molecules in the venoms of snakes from Colombia. However, we must continue conventionally studying the venom components, while “omics” technologies can be performed in a massive form and at a reasonable cost for Colombian researchers.

In human history there has always been a close link between snakes and human perception of life and death. Their venoms have been used in many forms, from enhancement for weapons to medieval remedies. From ancient civilitation to the present snake venoms had been useful to créate new molecules, from the firts antivenom to captopril a new durgs. The searches were carried out during april of 2021. We performed the searches following the prisma methods and recomendations. Snake venoms are a mix of active substances such enzymes, proteins, and peptides. The therapeutic properties that are attributed to venoms can be grouped into the following pharmacological uses: first alterations of the cardiovascular system and nervous system; and other indications such as cancer treatment, antimicrobial therapy, and management of coagulation disorders. The therapeutic potential of Colombian snake venoms is immense, and they can help generate new treatments for multiple pathologies. Using “omics” technologies will allow identifying more potential molecules in the venoms of snakes from Colombia. However, we must continue conventionally studying the venom components, while “omics” technologies can be performed in a massive form and at a reasonable cost for Colombian researchers.

1. From ancient potions to current drugs: A short trip in the history of the venoms used in medicine.

In human history there has always been a close link between snakes and human perception of life and death. Their venoms have been used in many forms, from enhancement for weapons to medieval remedies. Further, in some languages the same word is used both for life and for snake, it explain why in so many cultures snakes were seen as a healing creature or like a life-given God [1].

Since ancient civilizations snakes have been seen as a symbol of life and health. That explain why currently it is the symbol of medicine. In Mesoamerica cultures Quetzalcoatl (In Nahua, quetzalli means “bird” and “coatl” means snake) a feathered serpent, stands as a symbol for Earth and sky, time and space, fertility and creation, as well as guardian of snake medicine [2]. Today in the sierra of Jalisco, Mexico, traditional healers of the Wixárika community stay devout to the plumed serpent through song and dance [2].

On the other hand, in the Greek civilization, the snake represented the air, earth and was an attribute of Athena and its meaning was fecundity, health, continuity and eternity. It was told that in the temples of Asklepios at Epidaurus, Rhodes, Cnides, and Cos, the touch of the snake’s tongues could heal blind people. Besides, it is told that Aristotle described the properties of the venom and it uses [3]. He said that some vipers produce a venom that causes septic symptoms and immediate death, and other refer as asp make the skin got rotten. He also thought that poisonous animals ate another venomous animal to obtain its venom. Finally, he describes that some humans in Egypt and Libya used to obtain those venoms to poison other animals and enemies [4].

In Africa, ancient Egyptians represent the cycle of life, death, and resurrection in the Ouroboros symbol, which depicting a snake eating its own tail [5]. This ancient civilization referred snakes as Atoum, the creator of the air and the earth. Also, the golden cobra (Naja haje) named Uraeus, was the symbol of life, knowledge, and sovereignty [5]. It is said that Cleopatra was especially interested in snake venom effects [6]. She tested venoms on condemned prisoners to see the different reactions in the body and to find the toxic limits [6].

After Christianity and considering the Holy Bible bad reputation of snakes, it is clear why in Europe it was not frequently used the snake venom. There are only few references of it. One of them is an interesting tale from de 19th century, it is form the German chemist Kekulé (1829-1896), who on one of his dreams saw a snake with its tail in its mouth, later he related it to the structure of the benzene rings (aromatic rings composed by six carbon atoms used in the preparation dyes of detergents) [3].

The fascination by the toxicity of the snake venom has led humanity to use it for kill and to heal. The uses of the snake venoms can be summarized in two paths: as a weapon to defeat enemies in a silent way; and its role in therapies and remedies to heal the dying patients. One of the best-known weapons in which snake venom was used were arrows contaminated with venom. These weapons have its origins in the Greek mythology and was first used by Heracles. The venom dipped arrows were used by many ancient soldiers and warriors, from southern Africa to Siberia [3].

Since 326 BC when Alexander the Great was attacked in India with these lethal projectiles. The symptoms described by the soldiers suggested that it was poison from Russell’s viper (Daboia russelii). Later in the V century BC, Scynthian warriors used venom as coating for arrow tips with the purpose to kill enemies. Nevertheless, this culture went further by exploring the venom healing properties. Some ancient writings describe the technique employed by Scynthian to obtain the venoms with the purpose of creating antivenoms and medicines [7].

Scynthian healer named Agari joined the King Mithridates (will be covered later) to research on the snake venoms. They came to the conclusion that the venom could be digested in smalls amounts, but that it was lethal if it enters to the bloodstream [8].

Also, they used to say that every poisonous substance has its natural antidote. That is why they commonly combined ingredients such cinnamon, honey, castor, garlic, charcoal, among others with the snake venom to create the treatment. Additionally, one common use was the electuary, it was a paste made with honey and a minute amount of venom and alongside with the Theriac (=Theriaque) it was believe that may boost the immune system [9].

Finally, the snake venom was also use to treat war wounds and hemorrhages for its anticoagulant properties [10].

Similarly, Cathaginian Hannibal Barca (247-181 BC), general who led the fight against of the Roman republic during the Second Punic War, once ordered his soldiers to throw pots full of snakes at enemy ships causing great damage to them. However, this biological attack led to the creation of the first "antivenom" by mixing the snake meat with a variety of components and was named "Theriaque" [7].

On the other hand, in the Black Sea empire in the first century BC, using the same Cleopatra’s methodological approaches, the king Mithridates VI of Pontus (120–63 BC) known as the first toxicologist formulated a universal antidote that contained a mix of toxins and antidotes. The King Mithridates proclaimed himself the discoverer of the antidote ("Theriaque") useful in the treatment for every venomous reptile and poisonous substance. He also used prisoners to explore antidotes to face snake envenoming [11].

Table 1. Biological activities of some snake venom toxins and their pharmacological potential

On the other hand, in the Black Sea empire in the first century BC, using the same Cleopatra’s methodological approaches, the king Mithridates VI of Pontus (120–63 BC) known as the first toxicologist formulated a universal antidote that contained a mix of toxins and antidotes. The King Mithridates proclaimed himself the discoverer of the antidote ("Theriaque") useful in the treatment for every venomous reptile and poisonous substance. He also used prisoners to explore antidotes to face snake envenoming [11].