tetano
Editor, Senior Moderator
Cell Rep
. 2020 May 30;107774.
doi: 10.1016/j.celrep.2020.107774. Online ahead of print.
Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex From SARS-CoV-2
Qi Peng[SUP] 1 [/SUP], Ruchao Peng[SUP] 1 [/SUP], Bin Yuan[SUP] 2 [/SUP], Jingru Zhao[SUP] 2 [/SUP], Min Wang[SUP] 1 [/SUP], Xixi Wang[SUP] 1 [/SUP], Qian Wang[SUP] 2 [/SUP], Yan Sun[SUP] 3 [/SUP], Zheng Fan[SUP] 1 [/SUP], Jianxun Qi[SUP] 4 [/SUP], George F Gao[SUP] 4 [/SUP], Yi Shi[SUP] 5 [/SUP]
Affiliations
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.
Keywords: RNA synthesis; SARS-CoV-2; cofactors; cryo-EM; non-structural proteins; polymerase.
. 2020 May 30;107774.
doi: 10.1016/j.celrep.2020.107774. Online ahead of print.
Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex From SARS-CoV-2
Qi Peng[SUP] 1 [/SUP], Ruchao Peng[SUP] 1 [/SUP], Bin Yuan[SUP] 2 [/SUP], Jingru Zhao[SUP] 2 [/SUP], Min Wang[SUP] 1 [/SUP], Xixi Wang[SUP] 1 [/SUP], Qian Wang[SUP] 2 [/SUP], Yan Sun[SUP] 3 [/SUP], Zheng Fan[SUP] 1 [/SUP], Jianxun Qi[SUP] 4 [/SUP], George F Gao[SUP] 4 [/SUP], Yi Shi[SUP] 5 [/SUP]
Affiliations
- PMID: 32531208
- PMCID: PMC7260489
- DOI: 10.1016/j.celrep.2020.107774
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.
Keywords: RNA synthesis; SARS-CoV-2; cofactors; cryo-EM; non-structural proteins; polymerase.