Science (American Association for the Advancement of Science), 2020-06, Vol.368 (6497), p.1331-1335
2020
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- Autor(en) / Beteiligte
- Titel
- Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease
- Ist Teil von
- Science (American Association for the Advancement of Science), 2020-06, Vol.368 (6497), p.1331-1335
- Ort / Verlag
- United States: The American Association for the Advancement of Science
- Erscheinungsjahr
- 2020
- Quelle
- American Association for the Advancement of Science
- Beschreibungen/Notizen
- SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the etiological agent responsible for the global COVID-19 (coronavirus disease 2019) outbreak. The main protease of SARS-CoV-2, M , is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds ( and ) targeting M Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The x-ray crystal structures of SARS-CoV-2 M in complex with or , both determined at a resolution of 1.5 angstroms, showed that the aldehyde groups of and are covalently bound to cysteine 145 of M Both compounds showed good pharmacokinetic properties in vivo, and also exhibited low toxicity, which suggests that these compounds are promising drug candidates.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.abb4489Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7179937
- Format
- –
- Schlagworte
- Aldehydes, Animals, Antiviral activity, Antiviral Agents - chemistry, Antiviral Agents - pharmacology, Betacoronavirus - drug effects, Betacoronavirus - enzymology, Biochem, Biocompatibility, Catalytic Domain, Cell culture, Chlorocebus aethiops, Coronaviridae, Coronavirus 3C Proteases, Coronavirus Infections - drug therapy, Coronaviruses, COVID-19, Crystal structure, Cysteine Endopeptidases, Dogs, Drug Design, Drug development, Drug Evaluation, Preclinical, Etiology, Female, Humans, Lead compounds, Male, Mice, Molecular Structure, Pandemics, Pharmacokinetics, Pharmacology, Pneumonia, Viral - drug therapy, Protease, Protease inhibitors, Protein Structure, Tertiary, Proteinase inhibitors, Racing, Rats, Sprague-Dawley, Replication, Respiratory diseases, SARS-CoV-2, Severe acute respiratory syndrome, Severe acute respiratory syndrome coronavirus 2, Therapeutic targets, Toxicity, Toxicity testing, Toxicity Tests, Transcription, Vaccines, Vero Cells, Viral diseases, Viral Nonstructural Proteins - antagonists & inhibitors, Viruses