Crystal Structure of Non-Structural Protein 10 from Severe Acute Respiratory Syndrome Coronavirus-2

Int J Mol Sci. 2020 Oct 6;21(19):7375. 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 Å 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.

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Molecular Dynamics Simulation*
  • Protein Binding
  • S-Adenosylmethionine / chemistry
  • S-Adenosylmethionine / metabolism
  • Sequence Homology
  • Viral Regulatory and Accessory Proteins / chemistry*
  • Viral Regulatory and Accessory Proteins / metabolism
  • Zinc Fingers

Substances

  • NSP10 protein, SARS-CoV-2
  • Viral Regulatory and Accessory Proteins
  • S-Adenosylmethionine