Günther, S.; Reinke, P.Y.A.; Fernández-Garciá, Y.; Lieske, J.; Lane, T.J. et al.: X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease. In: Science 372 (2021), Nr. 6542, S. 642-646. DOI: https://doi.org/10.1126/science.abf7945
Abstract: | |
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. | |
License of this version: | CC BY 4.0 Unported |
Document Type: | Article |
Publishing status: | publishedVersion |
Issue Date: | 2021 |
Appears in Collections: | Naturwissenschaftliche Fakultät |
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