Alpha ketoamide stopped the multiplication of coronavirus

Scientists have improved the alpha ketoamide which disturb the activity of the main protease of the virus SARS-CoV-2. This has got crystal structure of viral protein and its complex with inhibitor. New substances live longer in human cells, and testing on mice showed that the drug enters the lungs and is retained in them. Inhalation of alpha-ketoamides did not cause side effects and based on of these substances to develop drugs against the new virus. Article published in the journal Science.

The coronavirus, which has led to a pandemic of diseases COVID-19, received the name of SARS-CoV-2. The fact that a new virus similar to the causative agent of SARS, SARS-CoV that caused the epidemic in 2003. Neither the flash, nor after it was not brought about clinical trials of a drug that would destroy the virus, and in 2020, humanity is once again faced with the need to come up with a treatment.

To create a substance that suppresses the activity of the virus, you need to define the target molecule and its plot, which medicine could attack. The well-studied coronaviruses , the main protease — this protein breaks down long amino acid chains into shorter pieces, which then turn out viral proteins. If you block the work of the main protease, the virus can not produce new proteins, and hence to reproduce. Own protease of a man cut other amino acid sequence, therefore, the inhibitor of viral protein will not disrupt their work, and the drug will not be toxic.

More by February 2020 a group of scientists has created a series of alpha-ketoamide, which inhibited the main proteases of coronaviruses of different genera. Now scientists from Germany and China under the leadership of Lingling Csana (Linlin Zhang) from the University of Lubeck have increased the viability of these molecules in human cells. This changed the structure of the substance, moving the important parts of the molecule in the position in which they will be unavailable for cellular proteases, and increasing the solubility ketoamides.

The researchers then determined the three dimensional crystal structure of the main protease SARS-CoV-2, to test how the new alpha ketoamide spatially compatible with their target. The molecule is modified so that the specific inhibition of SARS coronavirus was highest in the greatest life expectancy substances in the cell.

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