Researchers indentify a cell-permeable peptide that inhibits hepatitis C

January 31, 2012, University of California - Los Angeles

Researchers from UCLA's Jonsson Comprehensive Cancer Center have identified a cell-permeable peptide that inhibits a hepatitis C virus protein and blocks viral replication, which can lead to liver cancer and cirrhosis.

This finding by Dr. Samuel French, an assistant professor of pathology and senior author of the study, builds on previous work by the French laboratory that identified two that are important factors in infection.

French and his team initially set out to identify the cellular factors involved in hepatitis C replication and, using , found that (HSPs) 40 and 70 were important for viral infection. HSP70 was previously known to be involved, but HSP40 was linked for the first time to , French said. They further showed that the Quercetin, which inhibits the synthesis of these proteins, significantly inhibits viral infection in tissue culture.

In this study, published Jan. 30, 2012 in the peer-reviewed journal Hepatology, French and his team demonstrated that the viral non-structural protein 5A (NS5A) directly binds to HSP70 and mapped the site of the NS5A/HSP70 complex on NS5A. While HSP70 was previously shown to bind NS5A in cells, a direct NS5A/HSP70 interaction and complex formation was established in this study. In an effort to stop this interaction, they tested peptides that might inhibit HSP70.

"This is important because we've developed a small peptide that binds to that site and blocks the interaction between the proteins that is important for ," French said. "This is another, potentially highly efficacious way to block replication of hepatitis C."

An estimated 160 million people worldwide are infected with hepatitis C and the conventional treatments – interferon and ribavirin – can have significant side effects. A new drug targeting cellular proteins rather than viral proteins would be a valuable addition to the treatment arsenal, French said.

"We were surprised that this peptide works this well," French said. "While its mechanism is different, the activity of this peptide is comparable to other newly developed anti-virals."

The study, done in tissue culture, shows that the peptide gains entry into the cell easily and blocks the cascade of cellular events that allows the virus to replicate, French said. Blocking the HSP70 protein rather than a viral protein also reduces the chance of patients with the hepatitis C virus developing resistance to the peptide.

"There's no direct pressure on the virus, so it is less likely to mutate and develop resistance," French said. "The goal is to achieve a sustained response, essentially a cure, meaning there is no more virus replication. There are a lot of drugs coming out now that are designed to stop hepatitis C replication, but resistance is still an issue. About 10 to 20 percent of patients on the new drugs become resistant. This new peptide may help combat resistance."

Going forward, French and his team are testing variants of the newly discovered peptide to see if they can develop one with an even higher affinity and can decrease the size of the peptide to improve cellular penetration and liver targeting. The new and improved peptides will be tested in animal models.

This peptide "may be a candidate for therapy," the study states. "Considering the potency of the peptide in suppressing viral translation levels, treatment with this peptide may significantly improve the efficacy of conventional treatments in patients who become resistant to conventional therapies."

Explore further: New compounds show promise against hepatitis C infection

Related Stories

New compounds show promise against hepatitis C infection

April 12, 2011
Two bioflavonoids, catechin and naringenin, have displayed antiviral activity on tissue culture infected with Hepatitis C.

Recommended for you

New long-acting approach for malaria therapy developed

January 22, 2018
A new study, published in Nature Communications, conducted by the University of Liverpool and the Johns Hopkins University School of Medicine highlights a new 'long acting' medicine for the prevention of malaria.

Virus shown to be likely cause of mystery polio-like illness

January 22, 2018
A major review by UNSW researchers has identified strong evidence that a virus called Enterovirus D68 is the cause of a mystery polio-like illness that has paralysed children in the US, Canada and Europe.

Creation of synthetic horsepox virus could lead to more effective smallpox vaccine

January 19, 2018
UAlberta researchers created a new synthetic virus that could lead to the development of a more effective vaccine against smallpox. The discovery demonstrates how techniques based on the use of synthetic DNA can be used to ...

Study ends debate over role of steroids in treating septic shock

January 19, 2018
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year.

New approach could help curtail hospitalizations due to influenza infection

January 18, 2018
More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014-15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help ...

Flu may be spread just by breathing, new study shows; coughing and sneezing not required

January 18, 2018
It is easier to spread the influenza virus (flu) than previously thought, according to a new University of Maryland-led study released today. People commonly believe that they can catch the flu by exposure to droplets from ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.