AI Article Synopsis
- The COVID-19 pandemic, caused by the SARS-CoV-2 virus, presents a significant global health challenge, with the viral main protease (M) identified as a key drug target due to its role in viral replication.
- Researchers have analyzed the x-ray structures of both the unbound SARS-CoV-2 main protease and its complex with a newly designed α-ketoamide inhibitor, which has been modified to improve its effectiveness.
- The optimized inhibitor shows a strong ability to target the lungs and is suitable for inhalation, making it a promising candidate for treating COVID-19.
Article Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a global health emergency. An attractive drug target among coronaviruses is the main protease (M, also called 3CL) because of its essential role in processing the polyproteins that are translated from the viral RNA. We report the x-ray structures of the unliganded SARS-CoV-2 M and its complex with an α-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compound in plasma. On the basis of the unliganded structure, we developed the lead compound into a potent inhibitor of the SARS-CoV-2 M The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.
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Source |
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164518 | PMC |
| http://dx.doi.org/10.1126/science.abb3405 | DOI Listing |
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