A Structural View of SARS-CoV-2 RNA Replication Machinery: RNA Synthesis, Proofreading and Final Capping

Cells. 2020 May 20;9(5):1267. doi: 10.3390/cells9051267.


The current coronavirus disease-2019 (COVID-19) pandemic is due to the novel coronavirus SARS-CoV-2. The scientific community has mounted a strong response by accelerating research and innovation, and has quickly set the foundation for understanding the molecular determinants of the disease for the development of targeted therapeutic interventions. The replication of the viral genome within the infected cells is a key stage of the SARS-CoV-2 life cycle. It is a complex process involving the action of several viral and host proteins in order to perform RNA polymerization, proofreading and final capping. This review provides an update of the structural and functional data on the key actors of the replicatory machinery of SARS-CoV-2, to fill the gaps in the currently available structural data, which is mainly obtained through homology modeling. Moreover, learning from similar viruses, we collect data from the literature to reconstruct the pattern of interactions among the protein actors of the SARS-CoV-2 RNA polymerase machinery. Here, an important role is played by co-factors such as Nsp8 and Nsp10, not only as allosteric activators but also as molecular connectors that hold the entire machinery together to enhance the efficiency of RNA replication.

Keywords: COVID19; RNA replication; SARS-CoV-2; infectious disease; protein structure.

Publication types

  • Review

MeSH terms

  • Animals
  • Betacoronavirus / genetics*
  • COVID-19
  • Catalytic Domain
  • Coronavirus Infections / virology*
  • DNA-Directed RNA Polymerases / metabolism
  • Exoribonucleases / chemistry
  • Exoribonucleases / metabolism
  • Genome, Viral / genetics
  • Humans
  • Methyltransferases / chemistry
  • Methyltransferases / metabolism
  • Pandemics
  • Pneumonia, Viral / virology*
  • Protein Conformation, alpha-Helical
  • RNA Helicases / chemistry
  • RNA Helicases / metabolism
  • RNA, Messenger / metabolism
  • RNA, Viral / metabolism*
  • SARS-CoV-2
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / metabolism
  • Viral Regulatory and Accessory Proteins / chemistry
  • Viral Regulatory and Accessory Proteins / metabolism
  • Virus Replication / physiology*


  • NSP10 protein, SARS-CoV-2
  • RNA, Messenger
  • RNA, Viral
  • Viral Nonstructural Proteins
  • Viral Regulatory and Accessory Proteins
  • Methyltransferases
  • Nsp13 protein, SARS-CoV
  • Nsp16 protein, SARS virus
  • nsp14 protein, SARS coronavirus
  • DNA-Directed RNA Polymerases
  • Exoribonucleases
  • RNA Helicases