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A facile inhibitor screening of hepatitis C virus NS3 protein using nanoparticle-based RNA.

Roh C - Biosensors (Basel) (2012)

Bottom Line: We have previously shown that quantum dots (QDs)-conjugated RNA oligonucleotide can recognize the hepatitis C virus NS3 protein specifically and sensitively.Both 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone attenuated the binding affinity in a concentrated manner as evidenced by QDs conjugated RNA oligonucleotide.At a concentration of 0.01 μg·mL-1, 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone showed more than a 30% inhibition activity of a nanoparticle-based RNA oligonucleotide biochip system.

View Article: PubMed Central - PubMed

Affiliation: Division of Biotechnology, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), 1266, Sinjeong-dong, Jeongeup, Jeonbuk 580-185, Korea. chroh@kaeri.re.kr.

ABSTRACT
Globally, over hundreds of million people are infected with the hepatitis C virus: the global rate of death as a direct result of the hepatitis C virus has increased remarkably. For this reason, the development of efficient drug treatments for the biological effects of the hepatitis C virus is highly necessary. We have previously shown that quantum dots (QDs)-conjugated RNA oligonucleotide can recognize the hepatitis C virus NS3 protein specifically and sensitively. In this study, we elucidated that this biochip can analyze inhibitors to the hepatitis C virus NS3 protein using a nanoparticle-based RNA oligonucleotide. Among the polyphenolic compounds examined, 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone demonstrated a remarkable inhibition activity on the hepatitis C virus NS3 protein. Both 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone attenuated the binding affinity in a concentrated manner as evidenced by QDs conjugated RNA oligonucleotide. At a concentration of 0.01 μg·mL-1, 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone showed more than a 30% inhibition activity of a nanoparticle-based RNA oligonucleotide biochip system.

No MeSH data available.


Related in: MedlinePlus

Chemical structures of (A) 7,8,4'-trihydroxyisoflavone and (B) 6,7,4'-trihydroxyisoflavone.
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biosensors-02-00427-f002: Chemical structures of (A) 7,8,4'-trihydroxyisoflavone and (B) 6,7,4'-trihydroxyisoflavone.

Mentions: In Table 1, the effects of polyphenolic compounds on the inhibition of the hepatitis C virus NS3 protein used in this study are presented. Among the polyphenolic compounds screened, 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone showed high anti-viral activity. The chemical structures of 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone are shown in Figure 2. Figure 3 shows that both 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone had high inhibition activity in a concentrated manner against the hepatitis C virus NS3 protein. At a concentration of 0.01 μg·mL–1, 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone showed more than 30% inhibition activity of a QDs-RNA oligonucleotide biochip platform. As shown in Figure 3(A,B), 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone showed a similar pattern when comparing the concentration-dependent anti-viral activity. The half-maximal inhibitory concentration (IC50) values of 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone were found to be approximately 0.1 μg·mL–1 and 0.5 μg·mL–1, respectively (Figure 3(A,B)). Other polyphenolic compounds for the inhibition of the hepatitis C virus NS3 protein on the nanoparticle-based RNA oligonucleotide biochip system were detected as nearly similar to the background signal, due to the high affinity with the QDs-conjugated aptamer-hepatitis C virus NS3 protein (data not shown). To perform a high-throughput screening of the inhibitors, it would be efficient to be able to measure the anti-viral activity from optical images of a biochip containing multiple reaction compounds. The inhibition of the anti-viral activity from the hepatitis C virus NS3 protein was clearly illustrated and dose dependency was distinctly observable in the optical images. We demonstrated the specific interaction for inhibitor screening between RNA aptamer and HCV NS3 viral protein on biochip platform. We discovered a novel function of 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone as an antiviral agent. The discovery of antiviral drugs has been of considerable interest in developing efficient and sensitive methods for high-throughput screening in medicine. Furthermore, this proposed method can be considered a real-time monitoring method for inhibitor screening of HCV viral protein and is expected to be applicable to other types of diseases.


A facile inhibitor screening of hepatitis C virus NS3 protein using nanoparticle-based RNA.

Roh C - Biosensors (Basel) (2012)

Chemical structures of (A) 7,8,4'-trihydroxyisoflavone and (B) 6,7,4'-trihydroxyisoflavone.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263559&req=5

biosensors-02-00427-f002: Chemical structures of (A) 7,8,4'-trihydroxyisoflavone and (B) 6,7,4'-trihydroxyisoflavone.
Mentions: In Table 1, the effects of polyphenolic compounds on the inhibition of the hepatitis C virus NS3 protein used in this study are presented. Among the polyphenolic compounds screened, 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone showed high anti-viral activity. The chemical structures of 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone are shown in Figure 2. Figure 3 shows that both 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone had high inhibition activity in a concentrated manner against the hepatitis C virus NS3 protein. At a concentration of 0.01 μg·mL–1, 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone showed more than 30% inhibition activity of a QDs-RNA oligonucleotide biochip platform. As shown in Figure 3(A,B), 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone showed a similar pattern when comparing the concentration-dependent anti-viral activity. The half-maximal inhibitory concentration (IC50) values of 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone were found to be approximately 0.1 μg·mL–1 and 0.5 μg·mL–1, respectively (Figure 3(A,B)). Other polyphenolic compounds for the inhibition of the hepatitis C virus NS3 protein on the nanoparticle-based RNA oligonucleotide biochip system were detected as nearly similar to the background signal, due to the high affinity with the QDs-conjugated aptamer-hepatitis C virus NS3 protein (data not shown). To perform a high-throughput screening of the inhibitors, it would be efficient to be able to measure the anti-viral activity from optical images of a biochip containing multiple reaction compounds. The inhibition of the anti-viral activity from the hepatitis C virus NS3 protein was clearly illustrated and dose dependency was distinctly observable in the optical images. We demonstrated the specific interaction for inhibitor screening between RNA aptamer and HCV NS3 viral protein on biochip platform. We discovered a novel function of 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone as an antiviral agent. The discovery of antiviral drugs has been of considerable interest in developing efficient and sensitive methods for high-throughput screening in medicine. Furthermore, this proposed method can be considered a real-time monitoring method for inhibitor screening of HCV viral protein and is expected to be applicable to other types of diseases.

Bottom Line: We have previously shown that quantum dots (QDs)-conjugated RNA oligonucleotide can recognize the hepatitis C virus NS3 protein specifically and sensitively.Both 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone attenuated the binding affinity in a concentrated manner as evidenced by QDs conjugated RNA oligonucleotide.At a concentration of 0.01 μg·mL-1, 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone showed more than a 30% inhibition activity of a nanoparticle-based RNA oligonucleotide biochip system.

View Article: PubMed Central - PubMed

Affiliation: Division of Biotechnology, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), 1266, Sinjeong-dong, Jeongeup, Jeonbuk 580-185, Korea. chroh@kaeri.re.kr.

ABSTRACT
Globally, over hundreds of million people are infected with the hepatitis C virus: the global rate of death as a direct result of the hepatitis C virus has increased remarkably. For this reason, the development of efficient drug treatments for the biological effects of the hepatitis C virus is highly necessary. We have previously shown that quantum dots (QDs)-conjugated RNA oligonucleotide can recognize the hepatitis C virus NS3 protein specifically and sensitively. In this study, we elucidated that this biochip can analyze inhibitors to the hepatitis C virus NS3 protein using a nanoparticle-based RNA oligonucleotide. Among the polyphenolic compounds examined, 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone demonstrated a remarkable inhibition activity on the hepatitis C virus NS3 protein. Both 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone attenuated the binding affinity in a concentrated manner as evidenced by QDs conjugated RNA oligonucleotide. At a concentration of 0.01 μg·mL-1, 7,8,4'-trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone showed more than a 30% inhibition activity of a nanoparticle-based RNA oligonucleotide biochip system.

No MeSH data available.


Related in: MedlinePlus