Science (American Association for the Advancement of Science), 2020-05, Vol.368 (6492), p.779-782
2020
Details
- Autor(en) / Beteiligte
- Titel
- Structure of the RNA-dependent RNA polymerase from COVID-19 virus
- Ist Teil von
- Science (American Association for the Advancement of Science), 2020-05, Vol.368 (6492), p.779-782
- Ort / Verlag
- United States: The American Association for the Advancement of Science
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Science Online_科学在线
- Beschreibungen/Notizen
- A novel coronavirus [severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)] outbreak has caused a global coronavirus disease 2019 (COVID-19) pandemic, resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase [(RdRp), also named nsp12] is the central component of coronaviral replication and transcription machinery, and it appears to be a primary target for the antiviral drug remdesivir. We report the cryo-electron microscopy structure of COVID-19 virus full-length nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-angstrom resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified β-hairpin domain at its N terminus. A comparative analysis model shows how remdesivir binds to this polymerase. The structure provides a basis for the design of new antiviral therapeutics that target viral RdRp.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.abb7498Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7164392
- Format
- –
- Schlagworte
- Adenosine Monophosphate - analogs & derivatives, Adenosine Monophosphate - metabolism, Adenosine Monophosphate - pharmacology, Alanine - analogs & derivatives, Alanine - metabolism, Alanine - pharmacology, Antiviral Agents - metabolism, Antiviral Agents - pharmacology, Betacoronavirus - enzymology, Biochem, Catalytic Domain, Chemical synthesis, Cofactors, Comparative analysis, Coronaviridae, Coronavirus RNA-Dependent RNA Polymerase, Coronaviruses, COVID-19, Cryoelectron Microscopy, DNA-directed RNA polymerase, Drug Design, Electron microscopy, Microbio, Microscopy, Models, Molecular, Multiprotein Complexes - chemistry, Multiprotein Complexes - metabolism, Multiprotein Complexes - ultrastructure, Nucleotide analogs, Nucleotides, Pandemics, Protein Conformation, beta-Strand, Protein Domains, Replication, Respiratory diseases, RNA polymerase, RNA viruses, RNA-Dependent RNA Polymerase - antagonists & inhibitors, RNA-Dependent RNA Polymerase - chemistry, RNA-Dependent RNA Polymerase - metabolism, RNA-Dependent RNA Polymerase - ultrastructure, RNA-directed RNA polymerase, SARS-CoV-2, Severe acute respiratory syndrome, Severe acute respiratory syndrome coronavirus 2, Transcription, Viral diseases, Viral Nonstructural Proteins - antagonists & inhibitors, Viral Nonstructural Proteins - chemistry, Viral Nonstructural Proteins - metabolism, Viral Nonstructural Proteins - ultrastructure, Viruses