Article ; Online: Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2.
2020 Volume 31, Issue 11, Page(s) 107774
Abstract: ... of the SARS-CoV-2 polymerase complex consisting of the nsp12 catalytic subunit and nsp7-nsp8 cofactors ... of the core polymerase complex and lower thermostability of individual subunits of SARS-CoV-2 compared ... with SARS-CoV. These findings provide important insights into RNA synthesis by coronavirus polymerase and ...
| Abstract | The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has caused a huge number of human deaths. Currently, there are no specific drugs or vaccines available for this virus (SARS-CoV-2). The viral polymerase is a promising antiviral target. Here, we describe the near-atomic-resolution structure of the SARS-CoV-2 polymerase complex consisting of the nsp12 catalytic subunit and nsp7-nsp8 cofactors. This structure highly resembles the counterpart of SARS-CoV with conserved motifs for all viral RNA-dependent RNA polymerases and suggests a mechanism of activation by cofactors. Biochemical studies reveal reduced activity of the core polymerase complex and lower thermostability of individual subunits of SARS-CoV-2 compared with SARS-CoV. These findings provide important insights into RNA synthesis by coronavirus polymerase and indicate adaptation of SARS-CoV-2 toward humans with a relatively lower body temperature than the natural bat hosts. |
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| MeSH term(s) | Amino Acid Substitution ; Betacoronavirus/enzymology ; Coronavirus RNA-Dependent RNA Polymerase ; Cryoelectron Microscopy ; Escherichia coli/genetics ; Evolution, Molecular ; Models, Molecular ; Multiprotein Complexes/chemistry ; RNA-Dependent RNA Polymerase/chemistry ; RNA-Dependent RNA Polymerase/metabolism ; Severe acute respiratory syndrome-related coronavirus/enzymology ; SARS-CoV-2 ; Viral Nonstructural Proteins/chemistry ; Viral Nonstructural Proteins/metabolism |
| Chemical Substances | Multiprotein Complexes ; NS8 protein, SARS-CoV-2 ; Viral Nonstructural Proteins ; Coronavirus RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; NSP12 protein, SARS-CoV-2 (EC 2.7.7.48) ; NSP7 protein, SARS-CoV-2 (EC 2.7.7.48) ; RNA-Dependent RNA Polymerase (EC 2.7.7.48) |
| Keywords | covid19 |
| Language | English |
| Publishing date | 2020-05-30 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2649101-1 |
| ISSN | 2211-1247 ; 2211-1247 |
| ISSN (online) | 2211-1247 |
| ISSN | 2211-1247 |
| DOI | 10.1016/j.celrep.2020.107774 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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