Mutations in SARS-CoV-2 nsp7 and nsp8 proteins and their predicted impact on replication/transcription complex structure

J Med Virol. 2021 Jul;93(7):4616-4619. doi: 10.1002/jmv.26791. Epub 2021 Mar 14.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) has been identified to be a mutation hot spot, with the P323L mutation being commonly observed in viral genomes isolated from North America. RdRp forms a complex with nonstructural proteins nsp7 and nsp8 to form the minimal replication/transcription machinery required for genome replication. As mutations in RdRp may affect formation of the RdRp-nsp7-nsp8 supercomplex, we analyzed viral genomes to identify mutations in nsp7 and nsp8 protein sequences. Based on in silico analysis of predicted structures of the supercomplex comprising of native and mutated proteins, we demonstrate that specific mutations in nsp7 and nsp8 proteins may have a role in stabilization of the replication/transcription complex.

Keywords: RdRp; SARS-CoV-2; mutation; nsp7; nsp8.

MeSH terms

  • Amino Acid Sequence
  • Computer Simulation
  • Coronavirus RNA-Dependent RNA Polymerase / chemistry
  • Coronavirus RNA-Dependent RNA Polymerase / genetics*
  • Coronavirus RNA-Dependent RNA Polymerase / metabolism
  • Genome, Viral
  • Humans
  • Models, Molecular
  • Mutation
  • Protein Stability
  • SARS-CoV-2 / chemistry
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / physiology*
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / genetics*
  • Viral Nonstructural Proteins / metabolism
  • Viral Replication Compartments / chemistry*
  • Viral Replication Compartments / metabolism

Substances

  • NS8 protein, SARS-CoV-2
  • Viral Nonstructural Proteins
  • Coronavirus RNA-Dependent RNA Polymerase
  • NSP12 protein, SARS-CoV-2
  • NSP7 protein, SARS-CoV-2