Rattlesnake Venom Compounds Could Treat HCV

MARCH 09, 2018
Gail Connor Roche
Ana Carolina Gomes Jardim, PhDAna Carolina Gomes Jardim, PhD
Compounds found in rattlesnake venom show promise in fighting the hepatitis C virus (HCV).
        
A Brazil-based research team reported their discovery after isolating the neurotoxic complex crotoxin from the venom of Crotalus durissus terrificus, commonly known as the South American rattlesnake.
        
The researchers studied both crotoxin (CX) and 2 of its subunits, crotapotin (CP) and phospholipase A2 (PLA2-CB) to identify their effects on the HCV lifecycle.
        
"Our findings demonstrate for the first time the antiviral activity of compounds isolated from snake venom against hepatitis C virus," the study’s corresponding author, Ana Carolina Gomes Jardim, PhD, told MD Magazine. "These results may be useful for the development of future therapies."
        
Previous studies have shown that toxins in animal venoms exhibit antiviral activity against the yellow fever and dengue viruses, said Jardim, who heads the virology laboratory at Brazil’s Institute of Biomedical Sciences of the Federal University of Uberlandia (ICBIM-UFU). Hepatitis C belongs to the same Flaviviridae virus family as dengue and yellow fever, suggesting possible commonalities.

The team decided to test crotoxin, the main compound in the rattlesnake venom, and the 2 subunits singly and in combinations.

In a series of experiments, Jardim and colleagues from São Paulo State University, the University of Sao Paulo and other facilities considered the compounds’ antiviral effects on human cells to determine whether the substances could help prevent infection by HCV. 
        
The researchers also studied the impact of the compounds on the hepatitis C virus itself. Results were published in PLOS ONE and Scientific Reports.
        
"Our data demonstrated the multiple antiviral effects of toxins from animal venoms on HCV life cycle," the researchers wrote. "These toxins can inhibit different stages of the viral replicative cycle."
        
The team found that phospholipase inhibited the production of new viral particles by 86% compared with the particles’ production in the absence of the compound. The same experiment using crotoxin reduced viral particles by 58%, the results showed.
        
The scientists also worked to verify whether the compounds blocked the virus’s entry into cultured human cells. In this case, phospholipase blocked 97% of viral cell entry. Crotoxin reduced viral infection by 85%.

"Our results demonstrated the multiple antiviral effects of compounds isolated from Crotalus venom against HCV," Jardim said. ``PLA2-CB inhibited HCV entry and replication. CX reduced virus entry and release.’’
        
Crotapotin had no inhibitory effect on viral entry or replication, the results showed. However, crotapotin did affect another stage of the virus’s life cycle. It reduced the release of new viral particles from cells by 78%. In comparison, treatment with crotoxin achieved 50% inhibition of viral release.
        
Jardim said the finding that crotapotin inhibited the viral release step was surprising.
        
"This compound had not been described previously with antiviral activity," she said.
        
Asked about future research, Jardim said scientists are testing the compounds used in this study against other viruses. They’re also investigating additional compounds isolated from other species of snakes.
        
"Further analysis is needed to evaluate the effect of these compounds on other cell types and in vivo assays," she said.
        
It’s too early to know if these substances could become commercial virus-fighting products, Jardim said. For one thing, large-scale production would be required.
        
"But we believe that they have the potential," Jardim said.

The study, "Multiple effects of toxins isolated from Crotalus durissus terrificus on the hepatitis C virus life cycle," was published online in PLOSone.

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