Important step forward for Drug discovery: researchers discover vulnerability of Sars-CoV-2
A Frankfurt-based team of researchers has found out, such as Sars-CoV changed to 2 human cells, and a weak point in his mechanism identified. In the United States and Canada to start on the Basis of the findings even clinical studies for a possible active ingredient.
An interdisciplinary team of researchers from Frankfurt has found out, such as Sars-CoV changed to 2 human cells. The biochemists, and virologists to Sandra Ciesek used a specially for the new Coronavirus and developed a cell culture model. In it, they bred the Virus by using smears of two returnees from Wuhan in an intestinal cell line.
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The results show how an infection with Sars-CoV-2 runs in the host cells, While many viruses to the regular protein production of their host in favor of viral proteins to down, influenced by the new Coronavirus, the protein production of the host cells only a little. Instead, it seems that the viral proteins are not produced in competition to the proteins of the host cell. The Virus seems to increase the Protein lead to the synthesis machinery. A weak point, suspected by the researchers, and could actually with inhibitors of protein production (translation inhibitors), the propagation of the Virus, significantly reduce.
Cholesterol metabolism is reduced in RNA-manufacturing activity rises
24 hours after infection, the Virus causes Changes in the composition of the host cell proteins. The Cholesterol metabolism is reduced, at the same time, the activities in carbohydrate metabolism and in the production of RNA for protein production to increase. According to scientists, the Virus replication in the cultured cells successfully with inhibitors against these processes stop. Equally successful is the use of a compound that inhibits the production of new building blocks for viral genetic material was.
The scientists tested a series of compounds in model experiments in the laboratory, some of which slowed down the propagation of the Virus or stopped. These results make it possible to search for a drug on a small number of already authorised medicines to focus.
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First clinical trials starting in the United States and Canada
Since the beginning of the Corona-crisis usual, the Frankfurt researchers to make their findings immediately on a Preprint Server and on the website of the Institute for biochemistry II. Ivan Dikic, Director of the Institute, welcomed the latest development: “the culture of ‘Open Science, in which we share our scientific results as quickly as possible, as well as the interdisciplinary collaboration between biochemists and virologists have contributed to this success. The project was begun before, not even three months and already reveals new therapeutic approaches in Covid-19.“
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Because on the basis of the results of the Frankfurt researchers, both an American and a canadian company active ingredients for the clinical study prepare is now: one of the active ingredients, which stopped in the Frankfurt cell culture the multiplication of the virus, including 2-Deoxy-D-glucose (2-DG). This substance intervenes directly in the for the multiplication of the virus necessary for carbohydrate metabolism. The US company Moleculin Biotech has an active ingredient called WP1122, the 2-DG similar. On the Basis of a further in Frankfurt tested drug, Ribavirin, is launching the canadian company Bausch Health Americas, a clinical study with 50 subjects.
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“Great opportunity for the fight against the Virus”
Jindrich Cinatl from the Institute for Medical Virology and corresponding author, explained: “The successful use of drugs against Sars-CoV-2, which are components of already-approved drugs, is a great opportunity for the fight against the Virus. Such active substances are already well characterized, and we know, as they are well tolerated by patients. Therefore, being sought worldwide of such active ingredients. In a race with time, our work can provide an important contribution to this, in what directions, this search promises the fastest success.“
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