Short peptides derived from the interaction domain of SARS coronavirus nonstructural protein nsp10 can suppress the 2'-O-methyltransferase activity of nsp10/nsp16 complex

Virus Res. 2012 Aug;167(2):322-8. doi: 10.1016/j.virusres.2012.05.017. Epub 2012 May 29.


Coronaviruses are the etiological agents of respiratory and enteric diseases in humans and livestock, exemplified by the life-threatening severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV). However, effective means for combating coronaviruses are still lacking. The interaction between nonstructural protein (nsp) 10 and nsp16 has been demonstrated and the crystal structure of SARS-CoV nsp16/10 complex has been revealed. As nsp10 acts as an essential trigger to activate the 2'-O-methyltransferase activity of nsp16, short peptides derived from nsp10 may have inhibitory effect on viral 2'-O-methyltransferase activity. In this study, we revealed that the domain of aa 65-107 of nsp10 was sufficient for its interaction with nsp16 and the region of aa 42-120 in nsp10, which is larger than the interaction domain, was needed for stimulating the nsp16 2'-O-methyltransferase activity. We further showed that two short peptides derived from the interaction domain of nsp10 could inhibit the 2'-O-methyltransferase activity of SARS-CoV nsp16/10 complex, thus providing a novel strategy and proof-of-principle study for developing peptide inhibitors against SARS-CoV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / metabolism*
  • Methyltransferases / antagonists & inhibitors
  • Methyltransferases / metabolism*
  • Models, Molecular
  • Peptides / metabolism*
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping*
  • Severe acute respiratory syndrome-related coronavirus / enzymology*
  • Two-Hybrid System Techniques
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / metabolism*


  • Enzyme Inhibitors
  • Nsp10 protein, SARS virus
  • Peptides
  • Viral Nonstructural Proteins
  • Methyltransferases
  • Nsp16 protein, SARS virus