Short peptides derived from the interaction domain of SARS coronavirus nonstructural protein nsp10 can suppress the 2'-O-methyltransferase activity of nsp10/nsp16 complex.
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.
State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China.
Min
M
Ke
Yu
Y
Chen
Andong
A
Wu
Ying
Y
Sun
Ceyang
C
Su
Hao
H
Wu
Xu
X
Jin
Jiali
J
Tao
Yi
Y
Wang
Xiao
X
Ma
Ji-An
JA
Pan
Deyin
D
Guo
D004791:Enzyme Inhibitors / Q000378:metabolism*; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008958:Models, Molecular; D010455:Peptides / Q000378:metabolism*; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D045473:Severe acute respiratory syndrome-related coronavirus / Q000201:enzymology*; D020798:Two-Hybrid System Techniques; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; C558878:Nsp10 protein, SARS virus; D010455:Peptides; D017361:Viral Nonstructural Proteins; D008780:Methyltransferases; C558879:Nsp16 protein, SARS virus