Major protease blocked
March 23, 2020 at 11:57 am by Robert Klatt
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A new active ingredient was able to significantly inhibit the reproduction of the coronavirus in animal experiments and in human cell cultures. Due to the specific characteristics of the main protease, side effects and cell damage in humans can almost be excluded by this treatment approach.
Lübeck (Germany). Due to the exponentially increasing infections with the coronavirus, scientists worldwide are working on vaccines and medicines for the often fatal disease. In January researchers at the University of Marburg were able to present the molecule CR-31-B, which significantly inhibits the multiplication of the virus in cell cultures. In addition, the first clinical studies with the active ingredient remdesivir are being carried out in China and the U.S.A.
Another success story is coming from the University of Lübeck, whose scientists have developed a new starting point for an antiviral drug against the coronavirus, according to a publication in Science magazine. The group around Linlin Zhang and Rolf Hilgenfeld has decoded the structure of the main protease of the virus. It is the enzyme that the virus needs to have its RNA copied from the host cell. The virus produces polyproteins for this purpose, these are large protein complexes which the main protease then cuts into twelve smaller proteins. These building blocks then form the replication complex that starts the multiplication of viral RNA in the human body.
Virus replication can be prevented
As Hilgenfeld explains, “Virus replication can be prevented if the main protease can be blocked.” To decipher the enzyme, the Lübeck scientists used the genome of SARS-CoV-2, which was published in January by Chinese researchers. The recently introduced new gene scissors, which can also cut and manipulate virus RNA, have not yet been used. The researchers then synthesized the gene from the genetic construction instructions isolated from the genetic material and planted it into cell cultures of Escherichia coli bacteria.
Escherichia coli bacteria produce a viral enzyme
The manipulated Escherichia coli bacteria then began to produce larger amounts of the viral enzyme. As Zhang reports, “at the end of January, the scientists had cleaned and crystallized enough enzyme, which was then transported as crystals to the BESSY synchrotron in Berlin on February 1, to be brought into an intense X-ray beam there.” It is through X-ray diffraction possible to visualize the three-dimensional structure of the protease and even its individual atoms.
Decoding the protease accelerates inhibitor development
Deciphering the enzyme structure now opens up faster and more precise possibilities for science to develop and optimize inhibitors against the coronavirus. As the researchers explain, “inhibitors of this major viral protease are unlikely to be toxic because there is no human protease with similarly specific characteristics.” Cell damage and serious side effects are therefore very unlikely.
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