Science for Brazil (Reino Unido)

The truth behind ‘Snakebite Therapy’

Publicado em 17 fevereiro 2018

From the dusty cowboy bars of the old American West to the modern cities of South East Asia, there’s an enduring myth that a shot of rattlesnake whisky will give a man extra courage and virility. And today’s macho types flashing their rattlesnake cowboy boots in the bars of New York or Lost Angeles certainly perpetuate this legend.

So could there be truth in the idea that venomous reptiles could in some circumstances actually be beneficial to human health?

Scientists in Brazil – whose backlands are also home to some of the world’s most deadly reptiles – have discovered that compounds based on snake venom can indeed help to combat hepatitis C virus. The compounds – phospholipase and crotapotin – which are derived from the crotoxin in snake venom, can indeed block entry of the hepatitis virus into cultured human cells.

Scientists carried out a series of experiments, with results published in PLOS ONE, tested the antiviral properties of three compounds isolated from the venom of Crotalus durissus terrificus, the South American rattlesnake.

Two articles were authored by Brazilian scientists affiliated with São Paulo State University (UNESP), the Federal University of Uberlândia (UFU) and the University of São Paulo (USP). One paper describes very promising results for compounds that combat hepatitis C virus, while the second looks for plant-based compounds capable of the same task.

The research was conducted at UNESP’s Institute of Biosciences, Letters & Exact Sciences (IBILCE) in São José do Rio Preto, São Paulo State, by the Virology Group at the Genomic Studies Laboratory, led by Professor Paula Rahal, and at the Virology Laboratory of UFU’s Institute of Biomedical Sciences (ICBIM), led by Professor Ana Carolina Gomes Jardim. FAPESP provided funding of various types, as did the National Council for Scientific & Technological Development (CNPq), the Minas Gerais State Agency for Research and Development (FAPEMIG) and the Royal Society’s Newton Fund (UK).

“By treating cells with crotapotin, an antiviral effect was observed on HCV release, the only stage inhibited by this compound. Our data demonstrated the multiple antiviral effects of toxins from animal venoms on HCV life cycle,” the authors wrote.

The discovery is important for public health systems not only in Brazil but around the world that carry out very costly liver transplants – many of them on hepatitis B or C. For instance, hepatitis C patients alone account for 40% of all liver transplants in São Paulo.

The research originated from earlier scientific discovery that some compounds isolated from animal venom have shown activity against some viruses, such as dengue, yellow fever and measles.

The compounds from rattlesnake venom were isolated at the Toxicology Laboratory of USP’s School of Pharmaceutical Sciences in Ribeirão Preto, led by Professor Suely Vilela Sampaio.

The compounds were phospholipase A2 (PLA2-CB) and crotapotin (CP). In snake venom, they are associated with each other as subunits of the crotoxin protein complex, which the researchers also tested.

In a series of in vitro experiments with cultured human cells, they tested the antiviral action of the two compounds, both separately and together in the protein complex. They observed the compounds’ effects on human cells (to help prevent infection by the virus) and directly on hepatitis C virus.

The hepatitis C virus’s genome consists of a single strand of RNA (ribonucleic acid), which is a simple chain of nucleotides encoding the proteins in the virus.

“This virus invades the human host cell to replicate, producing new viral particles. Inside the host cell, the virus produces a complementary strand of RNA, from which molecules of viral genome will emerge to constitute the new particles,” Prof. Gomes Jardim told a Brazilian reporter.

“Our research showed that phospholipase can intercalate into double-stranded RNA, a virus replication intermediate, inhibiting the production of new viral particles. Intercalation reduced these by 86% compared with their production in the absence of phospholipase,” she said. When the same experiment was performed using crotoxin, production of viral particles fell 58%

The second stage of the research consisted of verifying whether the compounds blocked the virus’s entry into cultured human cells. In this case, the results were even more satisfactory: phospholipase blocked 97% of viral cell entry, and crotoxin reduced viral infection by 85%.

Lastly they tested crotapotin, another compound isolated from the same rattlesnake’s venom. Crotapotin had no inhibitory effect on viral entry or replication but did affect another stage of the virus’s life cycle, reducing release of new viral particles from cells by 78%. Treatment with crotoxin achieved 50% inhibition of viral release.

The second paper on the hunt for plant-based remedies to hepatitis C was published in Scientific Reports. It describes the action of chemical compounds against hepatitis C and was supported by FAPESP, CNPq, FAPEMIG and the Royal Society’s Newton Fund.

Two plant-based flavonoids that have already been shown to have antiviral action in experiments with dengue virus, were investigated. The authors tested the antiviral potential of the sorbifolin and pedalitin flavonoids derived from Pterogyne nitens, a tree known in Portuguese as amendoim-bravo. Flavonoids are compounds found in fruit, flowers, vegetables, honey and wine. The research was conducted by Professor Luis Octávio Regasini at UNESP’s Green & Medicinal Chemistry Laboratory in São José do Rio Preto.

To access the PLOS article, click here

To read a complete article on this topic by Brazilian journalist Peter Moon, click here