Venoms from Amazon snake and spider have pharmaceutical potential

Mapping of toxins from pit viper and tarantula reveals peptides that could lead in future to the development of novel drugs for cardiovascular problems and cancer, besides anti-bacterial, anti-fungal, and anti-viral potential.

By André Julião  |  Agência FAPESP – In studies supported by FAPESP, researchers at the Federal University of São Paulo (UNIFESP), the University of São Paulo (USP), and Butantan Institute have found the venom from a snake and spider endemic to the North of Brazil to contain a number of peptides – small fragments of proteins – with the pharmaceutical potential to combat heart problems, bacteria, fungi, viruses, and cancer, among other things.

The snake is Bothrops atrox, a highly venomous pit viper called jararaca-do-norte in Brazil and responsible for more human accidents involving snakes than any other species in the North region. The study of its venom is published in the Journal of Venomous Animals and Toxins including Tropical Diseases. 

The spider is Acanthoscurria rondoniae, a tarantula found in the Amazon. The study of its toxins is published in Frontiers in Pharmacology.

“We identified 105 peptides in the snake’s venom and 84 novel toxins expressed by the venom glands of the spider. Neither has been studied in such detail before. There are several studies of the snake species but they don’t deeply explore the peptides, which are small molecules comprising a few amino acids, making it easy for us to synthesize the ones we find most interesting,” said Alexandre Tashima, a professor at the Federal University of São Paulo’s Medical School (EPM-UNIFESP) and principal investigator for both studies, which were part of a project supported by FAPESP.

Animal venoms are known to have significant biotechnological potential. Venoms of the genus Bothrops, for example, contain toxins rich in bradykinin-potentiating peptides (BPPs), which have given rise to medications prescribed for the treatment of high blood pressure, such as captopril, a drug derived from peptides in the venom of B. jararaca.

US-based company Vestaron used the venom of a species of spider found in Australia (Hadronyche versuta) to produce a biopesticide that paralyzes crop-eating insects without affecting bees, birds or mammals.

In the study of B. atrox led by Tashima, the researchers set out to investigate the difference between venom from females and venom from males. They analyzed four individuals of each sex to test the hypothesis that the composition of venom from females is more powerful, possibly for evolutionary reasons and because they are larger than males.

“Depending on where they live and the prey available, venom composition may vary even within the same species,” Tashima said. “In the case of females, they have to protect their eggs and this may have favored selection of more powerful types of toxin.”

Corroborating the hypothesis, mass spectroscopy analysis showed female venom to contain higher levels of disintegrins, a family of small proteins that function as potent inhibitors of platelet aggregation and integrin-dependent cell adhesion. The researchers surmised that disintegrins in female venom may interfere even more with blood clotting than male venom, but further research is needed to test this theory. One of the novel disintegrins was characterized and labeled BATXDIS1.

The study also detected a number of BPPs in addition to those familiar from other species. Six of the 14 BPPs detected are novel molecules that can be studied in future and may give rise to new drugs to treat high blood pressure, for example.

Tarantula from Rondônia

Snakes have large venom glands that produce enough for researchers to characterize the venom and test its action, but spiders produce too little venom for this purpose, and recently developed computational tools have greatly facilitated research on this topic.

After characterizing venom from A. rondoniae (named after the Northern state of Rondônia) in the laboratory by various techniques, the researchers submitted the sequences obtained to open-access databases, using software to make the relevant comparisons. They found similarities among the 84 toxins analyzed with others that have bactericidal, anti-cancer, anti-fungal, and anti-viral properties. 

They also identified seven novel cysteine-rich peptides (CRPs), which are common in spider toxins and have well-known effects on ion channels and against bacteria. Besides these, another peptide has anti-fungal as well as bactericidal potential.

Some of the CRPs are very similar to peptides from other animals that have already proved promising against viruses. Two CRPs and four smaller peptides also showed potential against tumor cells.

The authors of the article stress that the findings are only indicative of potential biological activity. To confirm this activity, experiments should be conducted involving cellular and animal models. This is the next step planned by the researchers.

“The study also shows how little we know about Brazilian biodiversity, the largest in the world, both from the biological or ecological standpoint and in pharmacological and biotechnological terms,” Tashima said. “Molecules like these can be used sustainably. We’re losing many species without even knowing them.”

The article “Comparative gender peptidomics of Bothrops atrox venoms: are there differences between them?” by Adriana Simizo, Eduardo S. Kitano, Sávio S. Sant’Anna, Kathleen Fernandes Grego, Anita Mitico Tanaka-Azevedo and Alexandre K. Tashima can be read at: dx.doi.org/10.1590/1678-9199-jvatitd-2020-0055. 

The article “A multiomics approach unravels new toxins with possible in silico antimicrobial, antiviral, and antitumoral activities in the venom of Acanthoscurria rondoniae” by Guilherme A. Câmara, Milton Y. Nishiyama-Júnior, Eduardo S. Kitano, Ursula C. Oliveira, Pedro I. da Silva Júnior, Inácio L. Junqueira-de-Azevedo and Alexandre K. Tashima can be read at: www.frontiersin.org/articles/10.3389/fphar.2020.01075/full.