Format:
1 Online-Ressource
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Diagramme
ISSN:
1095-9203
Content:
The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for viral replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested alreadyapproved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.
Note:
Sonstige Körperschaft: Technische Universität Hamburg
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Sonstige Körperschaft: Technische Universität Hamburg,
In:
Science, Washington, DC : American Association for the Advancement of Science, 1880, 372(2021), 6542, Seite 642-646, 1095-9203
In:
volume:372
In:
year:2021
In:
number:6542
In:
pages: 642-646
Language:
English
DOI:
10.1126/science.abf7945
URN:
urn:nbn:de:gbv:830-882.0154742
URL:
https://doi.org/10.1126/science.abf7945
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