tetano
Editor, Senior Moderator
Int J Mol Sci
. 2020 Oct 6;21(19):E7375.
doi: 10.3390/ijms21197375.
Crystal Structure of Non-Structural Protein 10 from Severe Acute Respiratory Syndrome Coronavirus-2
Annika Rogstam[SUP] 1 [/SUP], Maria Nyblom[SUP] 1 [/SUP], Signe Christensen[SUP] 2 [/SUP], Celeste Sele[SUP] 1 [/SUP], Vladimir O Talibov[SUP] 3 [/SUP], Therese Lindvall[SUP] 1 [/SUP], Anna Andersson Rasmussen[SUP] 1 [/SUP], Ingemar Andr?[SUP] 2 [/SUP], Zo? Fisher[SUP] 1 4 [/SUP], Wolfgang Knecht[SUP] 1 [/SUP], Frank Kozielski[SUP] 5 [/SUP]
Affiliations
Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), causing Coronavirus Disease 19 (COVID-19), emerged at the end of 2019 and quickly spread to cause a global pandemic with severe socio-economic consequences. The early sequencing of its RNA genome revealed its high similarity to SARS, likely to have originated from bats. The SARS-CoV-2 non-structural protein 10 (nsp10) displays high sequence similarity with its SARS homologue, which binds to and stimulates the 3'-to-5' exoribonuclease and the 2'-O-methlytransferase activities of nsps 14 and 16, respectively. Here, we report the biophysical characterization and 1.6 ? resolution structure of the unbound form of nsp10 from SARS-CoV-2 and compare it to the structures of its SARS homologue and the complex-bound form with nsp16 from SARS-CoV-2. The crystal structure and solution behaviour of nsp10 will not only form the basis for understanding the role of SARS-CoV-2 nsp10 as a central player of the viral RNA capping apparatus, but will also serve as a basis for the development of inhibitors of nsp10, interfering with crucial functions of the replication-transcription complex and virus replication.
Keywords: COVID-19; RNA capping machinery; SARS CoV-2; non-structural proteins; nsp10; replication–transcription complex.
. 2020 Oct 6;21(19):E7375.
doi: 10.3390/ijms21197375.
Crystal Structure of Non-Structural Protein 10 from Severe Acute Respiratory Syndrome Coronavirus-2
Annika Rogstam[SUP] 1 [/SUP], Maria Nyblom[SUP] 1 [/SUP], Signe Christensen[SUP] 2 [/SUP], Celeste Sele[SUP] 1 [/SUP], Vladimir O Talibov[SUP] 3 [/SUP], Therese Lindvall[SUP] 1 [/SUP], Anna Andersson Rasmussen[SUP] 1 [/SUP], Ingemar Andr?[SUP] 2 [/SUP], Zo? Fisher[SUP] 1 4 [/SUP], Wolfgang Knecht[SUP] 1 [/SUP], Frank Kozielski[SUP] 5 [/SUP]
Affiliations
- PMID: 33036230
- DOI: 10.3390/ijms21197375
Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), causing Coronavirus Disease 19 (COVID-19), emerged at the end of 2019 and quickly spread to cause a global pandemic with severe socio-economic consequences. The early sequencing of its RNA genome revealed its high similarity to SARS, likely to have originated from bats. The SARS-CoV-2 non-structural protein 10 (nsp10) displays high sequence similarity with its SARS homologue, which binds to and stimulates the 3'-to-5' exoribonuclease and the 2'-O-methlytransferase activities of nsps 14 and 16, respectively. Here, we report the biophysical characterization and 1.6 ? resolution structure of the unbound form of nsp10 from SARS-CoV-2 and compare it to the structures of its SARS homologue and the complex-bound form with nsp16 from SARS-CoV-2. The crystal structure and solution behaviour of nsp10 will not only form the basis for understanding the role of SARS-CoV-2 nsp10 as a central player of the viral RNA capping apparatus, but will also serve as a basis for the development of inhibitors of nsp10, interfering with crucial functions of the replication-transcription complex and virus replication.
Keywords: COVID-19; RNA capping machinery; SARS CoV-2; non-structural proteins; nsp10; replication–transcription complex.