Designing and analysis of a potent bi-functional aptamers that inhibit protease and helicase activities of HCV NS3.
Nonstructural protein 3 (NS3) of hepatitis C virus (HCV) is a multi-functional enzyme having protease and helicase activities. NS3 is essential for HCV replication and proliferation. Previously, we obtained RNA aptamers against NS3 protease domain (Protease aptamer; deltaNEO-III and G9-II) and helicase domain (helicase aptamer; #5), and they inhibited the enzyme activities, respectively. We designed and constructed new bi-functional aptamers NEO-35-sX and G925-sX (X: 5-51 nts) by conjugating protease and helicase aptamers via oligo U spacer. Some of them showed 10-fold higher helicase inhibition than helicase aptamer #5 alone.
Umehara
Takuya
T
Institute of Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan.
Fukuda
Kotaro
K
Nishikawa
Fumiko
F
Sekiya
Satoru
S
Kohara
Michinori
M
Hasegawa
Tsunemi
T
Nishikawa
Satoshi
S
D000998:Antiviral Agents / Q000494:pharmacology*; D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D015195:Drug Design; D010450:Endopeptidases / Q000378:metabolism*; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology*; D020128:Inhibitory Concentration 50; D011480:Protease Inhibitors / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D020365:RNA Helicases / Q000037:antagonists & inhibitors*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D052157:Aptamers, Nucleotide; D010450:Endopeptidases; D011480:Protease Inhibitors; D020365:RNA Helicases; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases