Rocaglamide: modified medicinal plants against the hepatitis E virus
Hepatitis E virus (HEV) is the main cause of acute viral inflammation of the liver. Every year, about 20 million people around the world contract this disease and about 70,000 of them die. So far, there is no effective drug against the pathogen. But now rocaglamides from mahogany plants are raising hopes for the development of an antiviral drug.
Hepatitis E virus (HEV) is widespread. In this country, it is repeatedly detected in pork products. So far, there is no effective medicine against it. In this research, the so-called rocaglamides appeared: plant substances that can inhibit the reproduction of viruses. Researchers now report that a group of chemically modified rocaglamides have been shown to be particularly effective here. Their findings were published in the journal Antiviral Research.
Inhibitory effect on cancer cell proliferation
As explained in a recent release from Ruhr University Bochum (RUB), rocaglamides are a group of plants produced by various mahogany plants.
We already know that they have an inhibiting effect on the proliferation of certain cancer cells. It was not until 2008 that discoveries on their antiviral effect against RNA viruses were published for the first time: for example, they can inhibit the multiplication of the Ebola, HEV, Zika or even SARS-CoV-2 viruses. .
A Boston team led by Prof. Dr. John Porco Jr. has created a library of rocaglamides with various chemical modifications. "The core structure of the 205 substances is always the same, and different sized or flexible chemical groups have been attached to them," explains Mara Klöhn from the RUB.
205 substances tested for their effectiveness against HEV
The team led by Dimas F. Praditya, Mara Klöhn and Prof. Dr. Eike Steinmann from the RUB's Department of Molecular and Medical Virology tested their efficacy against HEV in cell culture.
To do this, the scientists used cancer cell lines and HEV genomes that were tagged with a reporter gene.
Based on the amount of protein produced, the blueprint of which is found in this reporter gene, researchers can measure exactly how successfully the virus multiplies in the presence of different substances.
Stronger effect than natural substance
Researchers use a so-called mean inhibitory concentration to indicate how well a substance inhibits virus replication. The lower it is, the better the substance works.
“The average inhibitory concentration of our three best-tested Rocaglamides is between 0.5 and 3 nanomolar”, explains Mara Klöhn. “For comparison: that of natural rocaglamide Silvestrol is three to seven nanomolar. One thing that these 3 main rocaglamides have in common is an attached amidino group.
Since rocaglamide also has a cell-killing effect, particularly noticeable in cancer cells, the experts also looked at this toxicity in healthy pig liver cells.
"Here, the toxicity was lower than in cell culture, which is based on cancer cell lines," says Klöhn. As stated in the communication, further studies should examine the efficacy and toxicity of the substances tested with the most success in the body.
We could also try to “chemically further optimize the best amidino-rocaglamides so that they are even more effective against viral replication”, specifies the researcher.
Main cause of acute viral inflammation of the liver
According to the announcement, the hepatitis E virus is the leading cause of acute viral inflammation of the liver. It is estimated that 20 million people around the world contract it every year, and about 70,000 of them die from it.
Normally, acute infections resolve on their own in people with an intact immune system. In people with weakened or suppressed immune systems, such as people who have had organ transplants or people infected with HIV, HEV can become chronic.
HEV is also particularly dangerous for pregnant women. Ribavirin is the only drug currently used, but it does not work in all cases. (ad)
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This text corresponds to the specifications of the specialized medical literature, medical guidelines and current studies and has been verified by health professionals.
Sources:Ruhr-Universität Bochum: Chemically modified plant substances are effective against the hepatitis E virus, (Accessed: June 28, 2022), Ruhr-Universität BochumDimas F. Praditya, Mara Klöhn, Yannick Brüggemann, Lauren E. Brown, John A. Porco, Jr., Wenhan Zhang, Volker Kinast, Andreas Kirschning, Florian WR Vondran, Daniel Todt, Eike Steinmann: Identification of structurally engineered rocaglites as inhibitors of hepatitis E virus replication; in: Antiviral research, (published: 06/18/2022), Antiviral research
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