Convincing impact: A new active ingredient could help with coronavirus outbreaks in the future. As a study suggests, the substance modeled on a natural plant substance successfully inhibits the multiplication of these pathogens. The compound also has an effect against other viruses such as Zika or Lassa – at least in cell experiments. However, whether and when the drug can be approved as a drug is still completely unclear.
The new corona virus is spreading more and more in China. Within a few days, the number of sufferers increased to over 7,000 cases, 170 patients died. The first cases are now also in the USA and Europe. In Germany, infection with the 2019 nCoV pathogen has been diagnosed in four patients so far.
With the increasing spread of the outbreak, the question of possible therapy options is becoming more urgent. While doctors have mainly treated symptomatically, researchers are looking for ways to directly combat coronaviruses. In fact, they have already found some active ingredients that show at least in laboratory tests against coronaviruses such as SARS and MERS-CoV.
Potent natural product
Christin Müller from the Justus Liebig University Gießen and her colleagues are now presenting another promising candidate. The starting point of her work was the natural product Silvestrol, which is found in Asian mahogany plants of the genus Aglaia. In Borneo, these plants are used as traditional remedies for a variety of diseases.
It was already known that Silvestrol also works against dangerous viruses – including corona viruses. Because the substance blocks an enzyme in body cells that the viruses need. They hijack the enzyme eIF4A and let it make its own proteins to multiply. The problem with this: “Unfortunately, Silvestrol is very difficult to produce chemically,” says co-author Arnold Grünweller from the Philipps University in Marburg. “So you have to use the plant again and again to gain the substance.”
Artificial counterpart in the test
In search of a more uncomplicated alternative, the scientists devoted themselves to an artificial counterpart to this natural product: the CR-31-B molecule on the one hand resembles the structure of Silvestrol. On the other hand, however, this compound is not quite as complex and has one chemical group less. As a result, it is easier to synthesize, but should still have the function important for the antiviral effect.
The researchers tested whether this was true on cells that had previously infected them with viruses. For the experiment, they added either Silvestrol or CR-31-B to the cultures. What would happen? In fact, the treatment showed that the virus concentration in the cells decreased sharply – regardless of which agent was used.
Broad effectiveness against viruses
“The antiviral effects are almost identical,” reports Müller. This finding was not only evident for corona viruses. Zika, Lassa and Crimean-Congo fever viruses also fought both remedies with similar success. Only against hepatitis E pathogens did the artificial inhibitor appear a little weaker than the natural one. “All in all, however, our results confirm that CR-31-B is as effective against a broad spectrum of viruses as Silvestrol,” Grünweller sums up.
However, it may take a while before patients are treated with the drug. “Molecules like CR-31-B, which have a broad spectrum antiviral effect similar to Silvestrol, are still a long way from being approved as a drug,” Grünweller emphasizes. The active ingredient therefore plays no role in the current outbreak of coronavirus.
Good opportunities for clinical trials
Nevertheless, the researchers are optimistic that drugs like CR-31-B will one day have effective weapons against coronaviruses. As they report, cancer medicine is already clinically testing a molecule that has many structural similarities with CR-31-B.
“This shows that this class of substances has no unexpected toxicity or mutagenicity in corresponding preclinical animal studies,” reports Grünweller. This will also simplify future clinical studies with CR-31-B, according to the scientist. (Antiviral Research, 2020; doi: 10.1016 / j.antiviral.2020.104706)
Source: Philipps University Marburg
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