Treat Hepatitis C With Compounds from Rattlesnake Venom

Highlights

• Compounds isolated from rattlesnake can fight against hepatitis C virus
• Two flavonoids such as phospholipase A2 (PLA2-CB) and crotapotin (CP) isolated from rattlesnake have antiviral action
• Phospholipase and crotapotin produce better results when used separately than together

A new approach helps isolate compounds from the venom of the South American rattlesnake to fight against of hepatitis C. Scientists investigated based on previous records in the scientific literature, where the animal venom was found to show activity against some viruses like yellow fever, measles, and dengue and the latter belongs to the same virus family as hepatitis’, the Flaviviridae family.

Currently, the therapies available are expensive, have adverse side effects, and cause viral resistance. There is an urgent need for new therapies to the fight against hepatitis C.

New Treatment for Hepatitis C

In the Sao Paulo State of Brazil, about 50 percent of liver transplants are performed on hepatitis B or C patients, revealed the state’s health department.

Hepatitis C patients alone account for about 40 percent of all liver transplants in São Paulo.

Scientists affiliated with the Institute of Biosciences, Letters & Exact Sciences, IBILCE of the São Paulo State University, UNESP (municipality of Sao Jose do Rio Preto’s campus), the Institute of Biomedical Sciences, ICBIM of the Federal University of Uberlandia, UFU and the School of Pharmaceutical Sciences of the University of Sao Paulo - USP (municipality of Ribeirao Preto’s campus).

Advertisement

Some funding institutions like FAPESP (Sao Paulo Research Foundation), CNPq (National Council for Scientific & Technological Development), Fapemig (Minas Gerais State Agency for Research and Development), and Newton Fund (Royal Society, UK) helped in conducting this study.

Scientists were able to test three compounds, which were taken from the venom of Crotalus durissus terrificus rattlesnake. They were also able to investigate the antiviral potential of flavonoids extracted from Pterogyne nitens, a kind of plant endemic to Brazil.

Advertisement

The results were published in PloS One and Scientific Reports.

What are the Compounds in Rattlesnake?

Two proteins such as phospholipase A2 (PLA2-CB) and crotapotin (CP) were isolated from the rattlesnake venom. Scientists also tested these compounds, as they are found in nature as subunits of the crotoxin protein complex in the Laboratory of Toxicology at FCF-USP.

The antiviral action of the two compounds was tested both separately and together in the protein complex in a series of in vitro experiments with cultured human cells.

Scientists observed the effects of compounds had on human cells (to help prevent infection by the virus) and also on hepatitis C virus.

The hepatitis C virus’s genome consists of a single strand of RNA (ribonucleic acid). It 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," said Ana Carolina Gomes Jardim, head of the Virology Laboratory in ICBIM-UFU.

Findings of the Study

"Our research showed that phospholipase could intercalate into double-stranded RNA, a virus replication intermediate, inhibiting the production of new viral particles. Intercalation reduced these by 86 percent compared with their production in the absence of phospholipase," said Jardim.

When the same experiment was conducted using crotoxin, production of viral particles decreased to 58 percent.

In the second stage of the research, scientists checked whether the compounds blocked the virus’s entry into cultured human cells or not.

In this case, the results were more than satisfactory: phospholipase blocked 97 percent of viral cell entry, and crotoxin reduced viral infection by 85 percent.

Finally, they tested crotapotin, which is another compound that has been isolated from the same rattlesnake’s venom.

Crotapotin had no inhibitory effect on viral entry or replication. However, it did affect another stage of the virus’s life cycle by reducing the release of new viral particles from cells by 78 percent. Treatment with crotoxin achieved 50 percent inhibition of viral release.

The results reveal that phospholipase and crotapotin produced better results when used separately than collectively.

Brazilian flora

The second article describes substances derived from Brazilian flora: sorbifolin and pedalitin, both flavonoids isolated from the leaves of Pterogyne nitens during the experiments, which was conducted by Professor Luis Octávio Regasini at UNESP’s Green & Medicinal Chemistry Laboratory in Sao José do Rio Preto.

Flavonoids are compounds that are usually found in fruit, flowers, vegetables, honey, and wine.

The flavonoids isolated from rattlesnake venom were tested for antiviral action in human cells that are infected with hepatitis C virus and in uninfected cells.

"Sorbifolin blocked viral entry into human cells in 45% of cases, while pedalitin provided more promising results, blocking entry in 79% of cases. The experiment was performed with two genotypes of hepatitis C virus: genotype 2A, the standard type in all studies, and genotype 3, the second most prevalent in Brazil. In both cases, the antiviral action of the flavonoids was equivalent," Gomes Jardim said.

However, at the other end of the viral life cycle, the flavonoids did not affect viral particle replication and also did not block their release from infected cells.

Paula Rahal, who coordinates the Virology Group at the Genomic Studies Laboratory at IBILCE-UNESP said that the flavonoids from P. nitens are among 200 tested compounds isolated from Brazilian plants or synthesized using natural structures by Professor Regasini.

These two flavonoids were tested against hepatitis C virus, as they were found to have antiviral action in experiments with dengue virus.



Source-Medindia