研究活動情報

• 2014年11月 細菌学会関西支部総会, 若手研究者奨励賞

  青木千恵

• Statins enhance extracellular release of hepatitis C virus particles through ERK5 activation.

  Chie Aoki-Utsubo, Masanori Kameoka, Lin Deng, Muhammad Hanafi, Beti Ernawati Dewi, Pratiwi Sudarmono, Takaji Wakita, Hak Hotta

  Statins, such as lovastatin, have been known to inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Statins were reported to moderately suppress hepatitis C virus (HCV) replication in cultured cells harboring HCV RNA replicons. We report here using an HCV cell culture (HCVcc) system that high concentrations of lovastatin (5-20 μg/mL) markedly enhanced the release of HCV infectious particles (virion) in the culture supernatants by up to 40 times, without enhancing HCV RNA replication, HCV protein synthesis, or HCV virion assembly in the cells. We also found that lovastatin increased the phosphorylation (activation) level of extracellular-signal-regulated kinase 5 (ERK5) in both the infected and uninfected cells in a dose-dependent manner. The lovastatin-mediated increase of HCV virion release was partially reversed by selective ERK5 inhibitors, BIX02189 and XMD8-92, or by ERK5 knockdown using small interfering RNA (siRNA). Moreover, we demonstrated that other cholesterol-lowering statins, but not dehydrolovastatin that is incapable of inhibiting HMG-CoA reductase and activating ERK5, enhanced HCV virion release to the same extent as observed with lovastatin. These results collectively suggest that statins markedly enhance HCV virion release from infected cells through HMG-CoA reductase inhibition and ERK5 activation.

  2024年07月, Microbiology and immunology, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Construction of Fosmid-based SARS-CoV-2 replicons for antiviral drug screening and replication analyses in biosafety level 2 facilities.

  Shunta Takazawa, Tomohiro Kotaki, Satsuki Nakamura, Chie Utsubo, Masanori Kameoka

  The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has necessitated the global development of countermeasures since its outbreak. However, current therapeutics and vaccines to stop the pandemic are insufficient and this is mainly because of the emergence of resistant variants, which requires the urgent development of new countermeasures, such as antiviral drugs. Replicons, self-replicating RNAs that do not produce virions, are a promising system for this purpose because they safely recreate viral replication, enabling antiviral screening in biosafety level (BSL)-2 facilities. We herein constructed three pCC2Fos-based RNA replicons lacking some open reading frames (ORF) of SARS-CoV-2: the Δorf2-8, Δorf2.4, and Δorf2 replicons, and validated their replication in Huh-7 cells. The functionalities of the Δorf2-8 and Δorf2.4 replicons for antiviral drug screening were also confirmed. We conducted puromycin selection following the construction of the Δorf2.4-puro replicon by inserting a puromycin-resistant gene into the Δorf2.4 replicon. We observed the more sustained replication of the Δorf2.4-puro replicon by puromycin pressure. The present results will contribute to the establishment of a safe and useful replicon system for analyzing SARS-CoV-2 replication mechanisms as well as the development of novel antiviral drugs in BSL-2 facilities.

  2023年09月, Virus research, 334, 199176 - 199176, 英語, 国際誌

  研究論文（学術雑誌）


• Identification of an Oligostilbene, Vaticanol B, from Dryobalanops aromatica Leaves as an Antiviral Compound against Hepatitis C Virus

  Chie Aoki-Utsubo, Muhammad Hanafi, Destia Tri Armanti, Hiroyuki Fuchino, Nobuo Kawahara, Sri Hartati, Aty Widyawaruyanti, Pratiwi Sudarmono, Masanori Kameoka, Hak Hotta

  Chronic hepatitis C virus (HCV) infection can lead to liver cirrhosis and hepatocellular carcinoma. Although current medications using direct-acting antivirals (DAAs) are highly effective and well-tolerated for treating patients with chronic HCV, high prices and the existence of DAA-resistant variants hamper treatment. There is thus a need for easily accessible antivirals with different mechanisms of action. During the screening of Indonesian medicinal plants for anti-HCV activity, we found that a crude extract of Dryobalanops aromatica leaves possessed strong antiviral activity against HCV. Bioassay-guided purification identified an oligostilbene, vaticanol B, as an active compound responsible for the anti-HCV activity. Vaticanol B inhibited HCV infection in a dose-dependent manner with 50% effective and cytotoxic concentrations of 3.6 and 559.5 µg/mL, respectively (Selectivity Index: 155.4). A time-of-addition study revealed that the infectivity of HCV virions was largely lost upon vaticanol B pretreatment. Also, the addition of vaticanol B following viral entry slightly but significantly suppressed HCV replication and HCV protein expression in HCV-infected and a subgenomic HCV replicon cells. Thus, the results clearly demonstrated that vaticanol B acted mainly on the viral entry step, while acting weakly on the post-entry step as well. Furthermore, co-treatment of the HCV NS5A inhibitor daclatasvir with vaticanol B increased the anti-HCV effect. Collectively, the present study has identified a plant-derived oligostilbene, vaticanol B, as a novel anti-HCV compound.

  2023年08月, Biol. Pharm. Bull., 46(8) (8), 1079 - 1087, 英語, 国内誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Amentoflavone inhibits hepatitis B virus infection via the suppression of preS1 binding to host cells.

  Chie Aoki-Utsubo, Puguh Indrasetiawan, Kento Fukano, Masamichi Muramatsu, Nina Artanti, Muhammad Hanafi, Hak Hotta, Masanori Kameoka

  Hepatitis B virus (HBV) is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Current therapeutic drugs for chronic HBV infection use IFN and nucleos(t)ide analogs; however, their efficacy is limited. Thus, there is an urgent need to develop new antivirals for HBV therapy. In this study, we identified a plant-derived polyphenolic bioflavonoid, amentoflavone, as a new anti-HBV compound. Amentoflavone treatment dose-dependently inhibited HBV infection in HBV-susceptible cells with HepG2-hNTCP-C4 and primary human hepatocyte PXB-cells. A mode-of-action study showed that amentoflavone inhibits the viral entry step, but not the viral internalization and early replication processes. Attachment of HBV particles as well as HBV preS1 peptide to HepG2-hNTCP-C4 cells was inhibited by amentoflavone. The transporter assay revealed that amentoflavone partly inhibits uptake of sodium taurocholate cotransporting polypeptide (NTCP)-mediated bile acid. Furthermore, effect of various amentoflavone analogs on HBs and HBe production from HBV-infected HepG2-hNTCP-C4 cells was examined. Robustaflavone exhibited comparable anti-HBV activity to that of amentoflavone and an amentoflavone-7,4', 4‴-trimethyl ether derivative (sciadopitysin) with moderate anti-HBV activity. Cupressuflavone or the monomeric flavonoid apigenin did not exhibit the antiviral activity. Amentoflavone and its structurally related biflavonoids may provide a potential drug scaffold in the design of a new anti-HBV drug inhibitor targeting NTCP.

  2023年03月, Microbiology and immunology, 英語, 国際誌

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Acacia mangium: A promising plant for isolating anti-hepatitis C virus agents

  Tutik Sri Wahyuni, Nida S. Sukma, Adita A. Permanasari, Chie Aoki-Utsubo, Aty Widyawaruyanti, Achmad Fuad Hafid

  Background: Medicinal plants have been demonstrated to possess various pharmacological effects including anti-hepatitis C virus. Acacia  mangium is one of the Acacia genus that contain with  various metabolites. The metaboilites play an  important role for antiviral activities. The current study examined the anti-hepatitis C virus (HCV) activities of Acacia mangium extracts in solvents with various polarities and further evaluated the mechanism of action of the extracts on the protein virus and combination treatment models.

  Methods: Anti-hepatitis C virus activities was conducted by in vitro culture cells of Huh 7it both in a single or combination treatment. Further examined its NS3 protein inhibition was evaluated by western blotting assay.

  Results: The results revealed the strong anti-HCV activities of the extracts. The 50% inhibition concentrations (IC₅₀s) of the ethanol, n-hexane, dichloromethane and methanol extracts were of 4.6 ± 0.3, 2.9 ± 0.2, 0.2 ± 0.3, and 2.8 ± 0.2 μg/mL, respectively, and no cytotoxic effect was detected. These extracts displayed stronger effects than the positive control ribavirin. The mode of action of the ethanol extract was evaluated at 30 µg/mL, revealing that the inhibitory effect was stronger on the post-entry step than on the entry step. Western blotting revealed that the extracts decreased NS3 protein expression, indicating that virus replication was suppressed. Further evaluation illustrated that combined treatment with the ethanol extract enhanced the anti-viral activity of simeprevir.

  Conclusions: These results indicated that A. mangium leaves could represent sources of anti-HCV agents.

  F1000 Research Ltd, 2023年02月, F1000Research, 11, 1452 - 1452

  研究論文（学術雑誌）


• An in vitro study of an Artocarpus heterophyllus substance as a hepatitis C antiviral and its combination with current anti-HCV drugs

  Adita Ayu Permanasari, Chie Aoki-Utsubo, Tutik Sri Wahyuni, Lidya Tumewu, Myrna Adianti, Aty Widyawaruyanti, Hak Hotta, Achmad Fuad Hafid

  Current therapy of chronic hepatitis C virus (HCV) with direct-acting antivirals (DAAs) has dramatically improved the sustained virologic response (SVR) of affected patients; however, treatment with DAAs remains expensive, and drug-resistant HCV variants remain a threat. As a result, there is still a need to continue to develop affordable and effective drugs for the treatment of HCV. Previously, we have demonstrated that a crude extract from Artocarpus heterophyllus leaves is a potential anti-HCV candidate. In this study, we have further purified this crude extract, examined which sub-fraction possesses the highest antiviral activity, and then explored its efficacy at different HCV life cycle stages. We also assessed synergistic antiviral effects between the A. heterophyllus extract and commercially available anti-HCV drugs. We used vacuum liquid chromatography (VLC) and high-performance liquid chromatography (HPLC) to fractionate a dichloromethane extract of A. heterophyllus leaves. We then examined the anti-HCV activity of the fractions using HCV genotype 2a, JFH1a; the antiviral mode of action was determined by exploring adding the treatments at different times. We examined the antiviral effects on the viral entry stage through a virucidal activity test, viral adsorption examination, and pretreatment of cells with the drug. The effects on the post-viral entry stage were determined by the levels of HCV protein expression and HCV RNA expression in infected cells. Through activity guided purification, we identified the sub-fraction FR3T3 as possessing the most robust anti-HCV activity with an IC₅₀ value of 4.7 ± 1.0 μg/mL. Mode-of-action analysis revealed that FR3T3 inhibited post-viral entry stages such as HCV NS3 protein expression and HCV RNA replication with marginal effects on the viral entry stage. Thin-layer Chromatography (TLC) indicated that FR3T3 contained terpenoids and chlorophyll-related compounds. We also found a synergistic antiviral activity when the DCM extract of A. heterohyllus was used in combination therapy with commercial anti-HCV drugs; Ribavirin, Simeprevir, Cyclosporin A. The extract of A. heterophyllus and its sub-fraction, FR3T3, presented here have anti-HCV activities and could be candidate drugs for add-on-therapy for treatment of chronic HCV infections.

  Springer Science and Business Media LLC, 2021年12月, BMC Complementary Medicine and Therapies, 21(1) (1)

  研究論文（学術雑誌）


• Alkaloid and benzopyran compounds of Melicope latifolia fruit exhibit anti-hepatitis C virus activities

  Aty Widyawaruyanti, Mulyadi Tanjung, Adita Ayu Permanasari, Ratih Saputri, Lidya Tumewu, Myrna Adianti, Chie Aoki-Utsubo, Hak Hotta, Achmad Fuad Hafid, Tutik Sri Wahyuni

  New agents for developing alternative or complementary medicine to treat the hepatitis C virus (HCV) are still needed due to high rates of HCV infection globally and the current limitations of available treatments. Treatment of HCV with a combination of direct acting antivirals have been shown to be approximately 90% effective but will be limited in the future due to the emergence of drug resistance and high cost. The leaves of Melicope latifolia have previously been reported to have anti-HCV activity and are a potential source of bioactive compounds for future novel drug development. This study aimed to evaluate the efficacy of the extract of M. latifolia fruit to treat HCV and to isolate its active compounds. M. latifolia fruit was extracted using methanol and purified using vacuum liquid chromatography (VLC) and Radial Chromatography. The anti-HCV activity was analyzed using cell culture lines Huh7it-1 and JFH1 (genotype 2a). Time-of-addition and immunoblotting studies were performed to identify the mode of action of the isolated active compounds. The structures of the active compounds were determined using nuclear magnetic resonance (NMR) spectra, UV, IR, and Mass Spectra. Six known compounds were isolated from M. latifolia fruit: O-methyloktadrenolon, alloevodionol, isopimpinellin, alloxanthoxyletin, methylevodionol, and N-methylflindersine. N-methylflidersine was the most active compound with IC₅₀ value of 3.8 μg/ml while methylevodionol, isopimpinellin, and alloevodionol were less active. O-methyloktadrenolon and alloxanthoxyletin were moderately active with IC₅₀ values of 10.9 and 21.72 μg/ml, respectively. N-methylflidersine decreased level of HCV NS3 protein expression in the cells. The alkaloid compound, N-methylflindersine which was isolated from M. latifolia possesses anti-HCV activity through post-entry inhibition and suppressed NS3 protein expression.

  Springer Science and Business Media LLC, 2021年12月, BMC Complementary Medicine and Therapies, 21(1) (1)

  研究論文（学術雑誌）


• Antiviral activity of Indonesian Medicinal Plants against hepatitis B virus.

  Wahyuni TS, Permanasari A, Widyawaruyanti A, Hotta H, Chie AU, Hafid A

  2020年, Pharmacognosy Journal, 12(5) (5), 1108 - 1114


• Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus

  Alaa M.H. El-Bitar, Moustafa Sarhan, Mohamed A. Abdel-Rahman, Veronica Quintero-Hernandez, Chie Aoki-Utsubo, Mohsen A. Moustafa, Lourival D. Possani, Hak Hotta

  © 2019, Springer Nature B.V. Growing global viral infections have been a serious public health problem in recent years. This current situation emphasizes the importance of developing more therapeutic antiviral compounds. Hepatitis C virus (HCV) and dengue virus (DENV) belong to the Flaviviridae family and are an increasing global health threat. Our previous study reported that the crude venom of Scorpio maurus palmatus possessed anti-HCV and anti-DENV activities in vitro. We report here the characterization of a natural antiviral peptide (scorpion-like peptide Smp76) that prevents HCV and DENV infection. Smp76 was purified from S. m. palmatus venom and contains 76 amino acids with six residues of cysteine. Smp76 antiviral activity was evaluated using a cell culture technique utilizing Huh7it-1, Vero/SLAM, HCV (JFH1, genotype 2a) and DENV (Trinidad 1751, type 2). A potential antiviral activity of Smp76 was detected in culture cells with an approximate IC50 of 0.01 μg/ml. Moreover, Smp76 prevents HCV infection and suppresses secondary infection, by inactivating extra-cellular infectious particles without affecting viral replication. Interestingly, Smp76 is neither toxic nor hemolytic in vitro at a concentration 1000-fold higher than that required for antiviral activity. Conclusively, this report highlights novel anti-HCV and anti-DENV activities of Smp76, which may lay the foundation for developing a new therapeutic intervention against these flaviviruses.

  Springer Science and Business Media LLC, 2019年01月, International Journal of Peptide Research and Therapeutics, 26(2) (2), 811 - 821

  研究論文（学術雑誌）


• Antiviral Activity of Cananga odorata Against Hepatitis B

  Indrasetiawan P, Aoki-Utsubo C, Hanafi M, Hartati S, Wahyuni TS, Kameoka M, Hotta H, Hayashi Y

  Chronic hepatitis B virus (HBV) infection can lead to liver cirrhosis and hepatocellular carcinoma. Current therapeutic drugs for chronic hepatitis B using pegylated interferons and nucleos(t)ide analogs have limited efficacy. Therefore, the development of novel and safe antivirals is required. Natural products including medicinal plants produce complex and structurally diverse compounds, some of which offer suitable targets for antiviral screening studies. In the present study, we screened various crude extracts from Indonesian plants for anti-HBV activity by determining their effects on the production of extracellular HBV DNA in Hep38.7-Tet cells and HBV entry onto a HBV-susceptible cell line, HepG2-NTCP, with the following results: (1) In Hep38.7-Tet cells, Cananga odorata exhibited the highest anti-HBV activity with a 50% inhibitory concentration (IC50) of 56.5 µg/ml and 50% cytotoxic concentration (CC50) of 540.2 µg/ml (Selectivity Index: 9.6). (2) The treatment of HepG2-NTCP cells with Cassia fistula, C. odorata, and Melastoma malabathricum at concentrations of 100 µg/ml lowered the levels of HBsAg production to 51.2%, 58.0%, and 40.1%, respectively, compared to untreated controls, and IC50 and CC50 values of C. odorata were 142.9 µg/ml and >400 µg/ml. In conclusion, the C. odorata extract could be a good candidate for the development of anti-HBV drugs.

  2019年, Kobe Journal of Medical Sciences, 65(2) (2), E71 - E79, 英語, 国内誌

  [査読有り]

  研究論文（学術雑誌）


• Antiviral Activities of Curcuma Genus against Hepatitis C Virus

  Wahyuni TS, Permatasari AA, Widiandani T, Fuad AH, Widyawaruyanti A, Aoki-Utsubo C, Hotta H

  2018年12月, NATURAL PRODUCT COMMUNICATIONS, 13(12) (12), 1579 - 1582

  [査読有り]


• Potential of Indonesian Plants (Annona muricata, Garcinia latissima, and Garcinia celebica) Against Hepatitis C Virus

  Apriyanto DR, Aoki-Utsubo C, Hartati S, Dewi BE, Hotta H

  2018年09月, ADVANCED SCIENCE LETTERS, 24(9) (9), 6807 - 6810

  [査読有り]


• Threonine-Allyl-Ester and Amide of Gallic Acid Derivative as Promising Anti-HCV Inhibitors

  Apriyanto DR, Arsianti A, Aoki-Utsubo C, Fadilah, Bahtiar A, Dwira S, Paramita RI, Hotta H

  2018年08月, ADVANCED SCIENCE LETTERS, 24(8) (8), 6265 - 6267

  [査読有り]


• Virucidal and Neutralizing Activity Tests for Antiviral Substances and Antibodies

  Aoki-Utsubo C, Chen M, Hotta H

  Bio-Protocol, LLC, 2018年05月, BIO-PROTOCOL, 8(10) (10)

  [査読有り]

  研究論文（学術雑誌）


• Time-of-addition and Temperature-shift Assays to Determine Particular Step(s) in the Viral Life Cycle that is Blocked by Antiviral Substance(s)

  Aoki-Utsubo C, Chen M, Hotta H

  2018年05月, BIO-PROTOCOL, 8(9) (9)

  [査読有り]


• Antiviral effect of archidendron pauciflorum leaves extract to hepatitis C virus: An in vitro study in JFH-1 strain

  Sri Hartati, Chie Aoki, Muhammad Hanafi, Marissa Angelina, Pratiwi Soedarmono, Hak Hotta

  Background: Hepatitis C virus (HCV) is a leading cause of chronic liver diseases. Drug resistance to the regimen is also increasing. Hence, there is a need for new anti-HCV agents that are less toxic and more efficacious. The aim of this study is to evaluate the possibility of A. pauciflorum extracts can be a antiviral drug. Methods: Huh-7it cells were infected with the HCV genotype 2a strain JFH-I in the presence of methanol extracts of Archidenron pauciflorum. The methanol extract further partition used n-hexane, ethyl acetate, n-butanol, and water showed in which butanol extracts exerted the strongest IC50 (6.3 g/ml). Further, the butanol fraction was fractionated and yielded into 13 fractions. Results: The methanol extract of the leaves of A. pauciflorum exhibited concentration dependent inhibition against the JFH1 strain of HCV genotype 2a with an IC50 is 72.5 μg/ml. The butanol fraction exhibited the highest anti-HCV activity with an IC50 is 6.3 μg/ml. The butanol fraction was fractionated which yielded 13 fractions. Fractions 5 and 13 exhibited high anti-HCV activities with IC50 is 5.0 μg/ml and 8.5 μg/ml and a time-of-addition study demonstrated that fraction 5 inhibited viral infection at the post-entry step, whereas fraction 13 primarily inhibited the viral entry step. Conclusion: The extract A. pauciflorum can be used as a herbal-based antiviral drug.

  Faculty of Medicine, Universitas Indonesia, 2018年03月, Medical Journal of Indonesia, 27(1) (1), 12 - 18, 英語

  [査読有り]

  研究論文（学術雑誌）


• Broad-spectrum antiviral agents: secreted phospholipase A(2) targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane

  Ming Chen, Chie Aoki-Utsubo, Masanori Kameoka, Lin Deng, Yutaka Terada, Wataru Kamitani, Kei Sato, Yoshio Koyanagi, Makoto Hijikata, Keiko Shindo, Takeshi Noda, Michinori Kohara, Hak Hotta

  Hepatitis C virus (HCV), dengue virus (DENV) and Japanese encephalitis virus (JEV) belong to the family Flaviviridae. Their viral particles have the envelope composed of viral proteins and a lipid bilayer acquired from budding through the endoplasmic reticulum (ER). The phospholipid content of the ER membrane differs from that of the plasma membrane (PM). The phospholipase A(2) (PLA(2)) superfamily consists of a large number of members that specifically catalyse the hydrolysis of phospholipids at a particular position. Here we show that the CM-II isoform of secreted PLA(2) obtained from Naja mossambica mossambica snake venom (CM-II-sPLA(2)) possesses potent virucidal (neutralising) activity against HCV, DENV and JEV, with 50% inhibitory concentrations (IC50) of 0.036, 0.31 and 1.34 ng/ ml, respectively. In contrast, the IC50 values of CM-II-sPLA(2) against viruses that bud through the PM (Sindbis virus, influenza virus and Sendai virus) or trans-Golgi network (TGN) (herpes simplex virus) were > 10,000 ng/ml. Moreover, the 50% cytotoxic (CC50) and haemolytic (HC50) concentrations of CMII- sPLA(2) were > 10,000 ng/ml, implying that CM-II-sPLA(2) did not significantly damage the PM. These results suggest that CM-II-sPLA(2) and its derivatives are good candidates for the development of broadspectrum antiviral drugs that target viral envelope lipid bilayers derived from the ER membrane.

  NATURE PUBLISHING GROUP, 2017年11月, SCIENTIFIC REPORTS, 7(1) (1), 15931, 英語

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Antiviral activity of the dichloromethane extracts from Artocarpus heterophyllus leaves against hepatitis C virus

  Achmad Fuad Hafid, Chie Aoki-Utsubo, Adita Ayu Permanasari, Myrna Adianti, Lydia Tumewu, Aty Widyawaruyanti, Sri Puji Astuti Wahyuningsih, Tutik Sri Wahyuni, Maria Inge Lusida, Soetjipto, Hak Hotta

  Objective To determine anti-viral activities of three Artocarpus species: Artocarpus altilis, Artocarpus camansi, and Artocarpus heterophyllus (A. heterophyllus) against Hepatitis C Virus (HCV). Methods Antiviral activities of the crude extracts were examined by cell culture method using Huh7it-1 cells and HCV genotype 2a strain JFH1. The mode of action for anti-HCV activities was determined by time-of-addition experiments. The effect on HCV RNA replication and HCV accumulation in cells were analyzed by quantitative reverse transcription-PCR and western blotting, respectively. Results The dichloromethane (DCM) extract of A. heterophyllus exhibited strong anti-HCV activity with an inhibitory concentration (IC50) value of (1.5 ± 0.6) μg/mL without obvious toxicity. The DCM extracts from Artocarpus altilis and Artocarpus camansi showed moderate anti-HCV activities with IC50 values being (6.5 ± 0.3) μg/mL and (9.7 ± 1.1) μg/mL, respectively. A time-of-addition studies showed that DCM extract from A. heterophyllus inhibited viral entry process though a direct virucidal activity and targeting host cells. HCV RNA replication and HCV protein expression were slightly reduced by the DCM treatment at high concentration. Conclusions The DCM extract from A. heterophyllus is a good candidate to develop an antiviral agent to prevent HCV grant reinfection following liver transplantation.

  Hainan Medical University, 2017年07月, Asian Pacific Journal of Tropical Biomedicine, 7(7) (7), 633 - 639, 英語

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Synthesis and anti-hepatitis C virus activity of gallic acid derivatives with chiral center

  Ade A, Aoki-Utsubo C, Fadilah F, Anton B, Dadan RA, Surya D, Novia AP, Hiroyuki T, Kiyomi K, Pratiwi S, Hak H, Rakia IP, Linda E

  2017年, Asian Journal of Pharmaceutical and Clinical Research, 10(7) (7), 164 - 167, 英語

  [査読有り]


• Anti-Hepatitis C Virus Activity of a Crude Extract from Longan (Dimocarpus longan Lour.) Leaves

  Dadan Ramadhan Apriyanto, Chie Aoki, Sri Hartati, Muhammad Hanafi, Leonardus Broto Sugeng Kardono, Ade Arsianti, Melva Louisa, Tjahjani Mirawati Sudiro, Beti Ernawati Dewi, Pratiwi Sudarmono, Amin Soebandrio, Hak Hotta

  Infection with hepatitis C virus (HCV) results in hepatitis C, a disease characterized by chronic infection, cirrhosis, and hepatocellular carcinoma. Currently, the standard therapy is a combination of pegylated interferon-alpha plus ribavirin with NS3 protease inhibitors. Addition of NS3 protease inhibitors to the standard therapy improves response rates; however, use of NS3 protease inhibitors is also associated with significant adverse effects and an increase in the overall cost of treatment. Therefore, there is a need to develop safe and inexpensive drugs for the treatment of HCV infections. In this study, we examined the antiviral activity of a crude extract from Dimocarpus longan leaves against HCV (genotype 2a strain JFH1). The D. longan crude extract (DL-CE) exhibited anti-HCV activity with a 50% effective concentration (EC50) of 19.4 mu g/ml without cytotoxicity. A time-of-addition study demonstrated that DL-CE has anti-HCV activity at both the entry and post-entry steps and markedly blocks the viral entry step through direct virucidal activity with marginal inhibition of virion assembly. Co-treatment of DL-CE with cyclosporine A, an immunosuppressant or telaprevir, an NS3 protease inhibitor, resulted in additive and synergistic antiviral effects, respectively. Our findings suggest that DL-CE may be useful as an add-on therapy candidate for treating HCV infections.

  NATL INST INFECTIOUS DISEASES, 2016年05月, JAPANESE JOURNAL OF INFECTIOUS DISEASES, 69(3) (3), 213 - 220, 英語

  [査読有り]

  研究論文（学術雑誌）


• AntiHepatitis C Virus Activity of Alectryon serratus Leaves Extract

  Lidya Tumewu, Evhy Apryani, Mei Ria Santi, Tutik Sri Wahyuni, Adita Ayu Permanasari, Myrna Adianti, Chie Aoki, Aty Widyawaruyanti, Achmad Fuad Hafid, Maria Inge Lusida, Soetjipto, Hak Hotta

  Hepatitis C Virus (HCV) has infected approximately 2-3% (130-170 million) of the world's population. No vaccine is available to prevent HCV infection. Investigation of anti-HCV agent is thus deemed necessary. Various plants have been explored for their anti-HCV activity. A. serratus is a member of Sapindaceae family, which fruit and seed were traditionally used as insecticide. Anti-HCV activity tested on A. serratus leaves extract has been done. The result showed that leaves extract exhibited anti-HCV with IC50 value of 14.9 mu g/ml and 9.8 mu g/ml against HCV J6/JFH1 and JFH1a, respectively. The cytotoxicity assay results showed that A. serratus leaves extract was not toxic and has CC50 > 100 mu g/ml. Mode of action experiment results suggested that A. serratus extract inhibited HCV at the post-entry step. Further fractionation of leaves extract by open column chromatography resulted in 4 fractions. Only Fraction 1 (AP-5F.1) exhibited anti-HCV with IC50 value of 1.2 mu g/ml against HCV JFH1a. Separation of AP-5F. 1 by open column chromatography resulted in 15 fractions. Fraction number 13 (AP-5F. 1.13) exhibited anti-HCV with IC50 value of 0.43 mu g/ml against HCV JFH1a. Separation of AP-5F. 1.13 by semi preparative-HPLC resulted in isolate identified by TLC and LC-MS method as chlorophyll derivate. There was a possibility that chlorophyll derivate has participated in performing the anti-HCV activity of fractions and extract besides the other compounds contained. In this study, we concluded that A. serratus leaves extract, AP-5F. 1, and AP-5F. 1.13 exhibited anti-HCV activity against JFH1a virus. (C) 2016 The Authors. Published by Elsevier B.V.

  ELSEVIER SCIENCE BV, 2016年, MOLECULAR AND CELLULAR LIFE SCIENCES: INFECTIOUS DISEASES, BIOCHEMISTRY AND STRUCTURAL BIOLOGY 2015 CONFERENCE, 18, 169 - 173, 英語

  [査読有り]

  研究論文（国際会議プロシーディングス）


• Activities of Ficus fistulosa Leave Extract and Fractions Against Hepatitis C Virus

  Achmad Fuad Hafid, Adita Ayu Permanasari, Lidya Tumewu, Myrna Adianti, Chie Aoki, Aty Widyawaruyanti, Soetjipto, Maria Inge Lusida, Hak Hotta

  Hepatitis C Virus (HCV) is a major global disease which often leads to chronicity and is potential to liver failure. There is no anti-HCV vaccine and the high diversity of viral genotypes will probably make it very difficult to develop a vaccine. Therefore, the development of new drugs for HCV treatment is highly required. It is commonly known that numerous important modern drugs have been developed from molecules originally isolated from natural sources. In this study, we tested the leave extract and fractions of Ficus fistulosa for their anti-HCV activities by cell culture method using Huh7it cells and HCV JFH1a. The result showed that ethanol extract of Ficus fistulosa (FFL) inhibited HCV JFH1a with IC50 value of 20.43 +/- 4.51 mu g/ml. Toxicity test also indicated that FFL was not toxic with CC50 value of > 200 mu g/ml. The extract was further fractionated using chloroform (FFLC) and butanol (FFLB) successively. FFLC showed anti-HCV activity with IC50 value of 5.67 +/- 1.54 mu g/ml and CC50 value of > 100 mu g/ml (Selectivity index > 17.65). Further separation of FFLC by open column chromatography resulted in 12 subfractions (FFLC1-C12). Two subfractions, FFLC10, and FFLC11 showed high selectivity index (> 100) with IC50 value of 0.60 +/- 0.30 mu g/ml and 0.43 +/- 0.29 mu g/ml, respectively. Therefore the leave extract (FFL) and fractions (FFL10, FFL11) of Ficus fistulosa would be a good candidate to develop antiviral against HCV. (C) 2016 The Authors. Published by Elsevier B.V.

  ELSEVIER SCIENCE BV, 2016年, MOLECULAR AND CELLULAR LIFE SCIENCES: INFECTIOUS DISEASES, BIOCHEMISTRY AND STRUCTURAL BIOLOGY 2015 CONFERENCE, 18, 179 - 184, 英語

  [査読有り]

  研究論文（国際会議プロシーディングス）


• Virocidal activity of Egyptian scorpion venoms against hepatitis C virus

  Alaa M. H. El-Bitar, Moustafa M. H. Sarhan, Chie Aoki, Yusuke Takahara, Mari Komoto, Lin Deng, Mohsen A. Moustafa, Hak Hotta

  Background: Hepatitis C virus (HCV) is a major global health problem, causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed. Recently, natural antimicrobial peptides (AMPs) are attracting more attention as biological compounds and can be a good template to develop therapeutic agents, including antiviral agents against a variety of viruses. Various AMPs have been characterized from the venom of different venomous animals including scorpions. Methods: The possible antiviral activities of crude venoms obtained from five Egyptian scorpion species (Leiurus quinquestriatus, Androctonus amoreuxi, A. australis, A. bicolor and Scorpio maurus palmatus) were evaluated by a cell culture method using Huh7.5 cells and the J6/JFH1-P47 strain of HCV. Time-of-addition experiments and inactivation of enzymatic activities of the venoms were carried out to determine the characteristics of the anti-HCV activities. Results: S. maurus palmatus and A. australis venoms showed anti-HCV activities, with 50% inhibitory concentrations (IC50) being 6.3 +/- 1.6 and 88.3 +/- 5.8 mu g/ml, respectively. S. maurus palmatus venom (30 mu g/ml) impaired HCV infectivity in culture medium, but not inside the cells, through virocidal effect. The anti-HCV activity of this venom was not inhibited by a metalloprotease inhibitor or heating at 60 degrees C. The antiviral activity was directed preferentially against HCV. Conclusions: S. maurus palmatus venom is considered as a good natural source for characterization and development of novel anti-HCV agents targeting the entry step. To our knowledge, this is the first report describing antiviral activities of Egyptian scorpion venoms against HCV, and may open a new approach towards discovering antiviral compounds derived from scorpion venoms.

  BIOMED CENTRAL LTD, 2015年03月, VIROLOGY JOURNAL, 12(1) (1), 47, 英語

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Inhibition of hepatitis C virus replication by chalepin and pseudane IX isolated from Ruta angustifolia leaves

  Tutik Sri Wahyuni, Aty Widyawaruyanti, Maria Inge Lusida, Achmad Fuad, Soetjipto, Hiroyuki Fuchino, Nobuo Kawahara, Yoshitake Hayashi, Chie Aoki, Hak Hotta

  Hepatitis C virus (HCV) infection is highly prevalent among global populations, with an estimated number of infected patients being 170 million. Approximately 70-80% of patients acutely infected with HCV will progress to chronic liver disease, such as liver cirrhosis and hepatocellular carcinoma, which is a substantial cause of morbidity and mortality worldwide. New therapies for HCV infection have been developed, however, the therapeutic efficacies still need to be improved. Medicinal plants are promising sources for antivirals against HCV. A variety of plants have been tested and proven to be beneficial as antiviral drug candidates against HCV. In this study, we examined extracts, their subfractions and isolated compounds of Ruta angustifolia leaves for antiviral activities against HCV in cell culture. We isolated six compounds, chalepin, scopoletin, gamma-fagarine, arborinine, kokusaginine and pseudane IX. Among them, chalepin and pseudane IX showed strong anti-HCV activities with 50% inhibitory concentration (IC50) of 1.7 +/- 0.5 and 1.4 +/- 0.2 mu g/ml, respectively, without apparent cytotoxicity. Their anti-HCV activities were stronger than that of ribavirin (2.8 +/- 0.4 mu g/ml), which has been widely used for the treatment of HCV infection. Mode-of-action analyses revealed that chalepin and pseudane IX inhibited HCV at the post-entry step and decreased the levels of HCV RNA replication and viral protein synthesis. We also observed that arborinine, kokusaginine and gamma-fagarine possessed moderate levels of anti-HCV activities with IC50 values being 6.4 +/- 0.7, 6.4 +/- 1.6 and 20.4 +/- 0.4 mu g/ml, respectively, whereas scopoletin did not exert significant anti-HCV activities at 30 mu g/ml. (C) 2014 Elsevier B.V. All rights reserved.

  ELSEVIER, 2014年12月, FITOTERAPIA, 99, 276 - 283, 英語

  [査読有り]

  研究論文（学術雑誌）


• Induction of Cell-Mediated Immune Responses in Mice by DNA Vaccines That Express Hepatitis C Virus NS3 Mutants Lacking Serine Protease and NTPase/RNA Helicase Activities

  Suratno Lulut Ratnoglik, Da-Peng Jiang, Chie Aoki, Pratiwi Sudarmono, Ikuo Shoji, Lin Deng, Hak Hotta

  Effective therapeutic vaccines against virus infection must induce sufficient levels of cell-mediated immune responses against the target viral epitopes and also must avoid concomitant risk factors, such as potential carcinogenic properties. The nonstructural protein 3 (NS3) of hepatitis C virus (HCV) carries a variety of CD4(+) and CD8(+) T cell epitopes, and induces strong HCV-specific T cell responses, which are correlated with viral clearance and resolution of acute HCV infection. On the other hand, NS3 possesses serine protease and nucleoside triphosphatase (NTPase)/RNA helicase activities, which not only play important roles in viral life cycle but also concomitantly interfere with host defense mechanisms by deregulating normal cellular functions. In this study, we constructed a series of DNA vaccines that express NS3 of HCV. To avoid the potential harm of NS3, we introduced mutations to the catalytic triad of the serine protease (H57A, D81A and S139A) and the NTPase/RNA helicase domain (K210N, F444A, R461Q and W501A) to eliminate the enzymatic activities. Immunization of BALB/c mice with each of the DNA vaccine candidates (pNS3[S139A/K210N], pNS3[S139A/F444A], pNS3[S139A/R461Q] and pNS3[S139A/W501A]) that expresses an NS3 mutant lacking both serine protease and NTPase/helicase activities induced T cell immune responses to the degree comparable to that induced by the wild type NS3 and the NS3/4A complex, as demonstrated by interferon-gamma production and cytotoxic T lymphocytes activities against NS3. The present study has demonstrated that plasmids expressing NS3 mutants, NS3(S139A/K210N), NS3(S139A/F444A), NS3(S139A/R461Q) and NS3(S139A/W501A), which lack both serine protease and NTPase/RNA helicase activities, would be good candidates for safe and efficient therapeutic DNA vaccines against HCV infection.

  PUBLIC LIBRARY SCIENCE, 2014年06月, PLOS ONE, 9(6) (6), e98877, 英語

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Anti-hepatitis C virus compounds obtained from Glycyrrhiza uralensis and other Glycyrrhiza species

  Myrna Adianti, Chie Aoki, Mari Komoto, Lin Deng, Ikuo Shoji, Tutik Sri Wahyuni, Maria Inge Lusida, Soetjipto, Hiroyuki Fuchino, Nobuo Kawahara, Hak Hotta

  Development of complementary and/or alternative drugs for treatment of hepatitis C virus (HCV) infection is still much needed from clinical and economic points of view. Antiviral substances obtained from medicinal plants are potentially good targets to study. Glycyrrhiza uralensis and G. glabra have been commonly used in both traditional and modern medicine. In this study, extracts of G. uralensis roots and their components were examined for anti-HCV activity using an HCV cell culture system. It was found that a methanol extract of G. uralensis roots and its chloroform fraction possess anti-HCV activity with 50%-inhibitory concentrations (IC50) of 20.0 and 8.0 mu g/mL, respectively. Through bioactivity-guided purification and structural analysis, glycycoumarin, glycyrin, glycyrol and liquiritigenin were isolated and identified as anti-HCV compounds, their IC50 being 8.8, 7.2, 4.6 and 16.4 mu g/mL, respectively. However, glycyrrhizin, the major constituent of G. uralensis, and its monoammonium salt, showed only marginal anti-HCV activity. It was also found that licochalcone A and glabridin, known to be exclusive constituents of G. inflata and G. glabra, respectively, did have anti-HCV activity, their IC50 being 2.5 and 6.2 mu g/mL, respectively. Another chalcone, isoliquiritigenin, also showed anti-HCV activity, with an IC50 of 3.7 mu g/mL. Time-of-addition analysis revealed that all Glycyrrhiza-derived anti-HCV compounds tested in this study act at the post-entry step. In conclusion, the present results suggest that glycycoumarin, glycyrin, glycyrol and liquiritigenin isolated from G. uralensis, as well as isoliquiritigenin, licochalcone A and glabridin, would be good candidates for seed compounds to develop antivirals against HCV.

  WILEY, 2014年03月, MICROBIOLOGY AND IMMUNOLOGY, 58(3) (3), 180 - 187, 英語

  [査読有り]

  研究論文（学術雑誌）


• Antiviral activity of extracts from Morinda citrifolia leaves and chlorophyll catabolites, pheophorbide a and pyropheophorbide a, against hepatitis C virus

  Suratno Lulut Ratnoglik, Chie Aoki, Pratiwi Sudarmono, Mari Komoto, Lin Deng, Ikuo Shoji, Hiroyuki Fuchino, Nobuo Kawahara, Hak Hotta

  The development of complementary and/or alternative drugs for treatment of hepatitis C virus (HCV) infection is still needed. Antiviral compounds in medicinal plants are potentially good targets to study. Morinda citrifolia is a common plant distributed widely in Indo-Pacific region; its fruits and leaves are food sources and are also used as a treatment in traditional medicine. In this study, using a HCV cell culture system, it was demonstrated that a methanol extract, its n-hexane, and ethyl acetate fractions from M. citrifolia leaves possess anti-HCV activities with 50%-inhibitory concentrations (IC50) of 20.6, 6.1, and 6.6 mu g/mL, respectively. Bioactivity-guided purification and structural analysis led to isolation and identification of pheophorbide a, the major catabolite of chlorophyll a, as an anti-HCV compound present in the extracts (IC50 = 0.3 mu g/mL). It was also found that pyropheophorbide a possesses anti-HCV activity (IC50 = 0.2 mu g/mL). The 50%-cytotoxic concentrations (CC50) of pheophorbide a and pyropheophorbide a were 10.0 and 7.2 mu g/mL, respectively, their selectivity indexes being 33 and 36, respectively. On the other hand, chlorophyll a, sodium copper chlorophyllin, and pheophytin a barely, or only marginally, exhibited anti-HCV activities. Time-of-addition analysis revealed that pheophorbide a and pyropheophorbide a act at both entry and the post-entry steps. The present results suggest that pheophorbide a and its related compounds would be good candidates for seed compounds for developing antivirals against HCV.

  WILEY-BLACKWELL, 2014年03月, MICROBIOLOGY AND IMMUNOLOGY, 58(3) (3), 188 - 194, 英語

  [査読有り]

  研究論文（学術雑誌）


• Isolation and identification of substances with anti-hepatitis c virus activities from kalanchoe pinnata

  Aoki Chie, Hartati Sri, Mei Ria Santi, Lydwina, Firdaus Rininta, Hanafi Muhammad, Kardono B.S. Leonardus, Shimizu Yohko, Sudarmono Pratiwi, Hotta Hak

  Objective: The aim of this study was to examine extracts from Indonesian plants to identify a compound(s) responsible for antiviral activity against hepatitis C virus (HCV). Methods: Huh7it-1 cells, a clone of human hepatocellular carcinoma-derived Huh7 cells, were infected with the HCV genotype 2a strain JFH1 in the presence of crude methanol extracts from the plants. The extracts were further fractionated and purified by anti-HCV bioactivity-guided analysis using a combination of various column chromatography techniques. The isolated compounds were examined for anti-HCV activity and cytotoxicity, and their structures determined by nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. Results: Screening of Indonesian plants revealed that a crude methanol extract from Kalanchoe pinnata exhibited anti-HCV activity with a 50%-inhibitory concentration (IC50) of 17.2 μg/ml. An ethyl acetate fraction was found to possess strong anti-HCV activity, from which three compounds, i.e., quercetin, gallic acid and quercitrin, were isolated. Anti-HCV activity assay revealed that quercetin and gallic acid, but not quercitrin, inhibited HCV production in a dose-dependent manner, with IC50 values of 1.5 and 6.1 μg/ml, respectively, without exhibiting cytotoxicity. A time-of-addition study demonstrated that quercetin acted at the post-entry step whereas gallic acid at both the entry and post-entry steps. Conclusion: An extract from K. pinnata and its constituents, quercetin and gallic acid, could be potentially used as a supplement for the treatment of HCV infection.

  2014年01月, International Journal of Pharmacy and Pharmaceutical Sciences, 6, 211 - 215

  [査読有り]


• Antiviral activities of Indonesian medicinal plants in the East Java region against hepatitis C virus

  Tutik Sri Wahyuni, Lydia Tumewu, Adita Ayu Permanasari, Evhy Apriani, Myrna Adianti, Abdul Rahman, Aty Widyawaruyanti, Maria Inge Lusida, Achmad Fuad, Soetjipto, Nasronudin, Hiroyuki Fuchino, Nobuo Kawahara, Ikuo Shoji, Lin Deng, Chie Aoki, Hak Hotta

  Background: Hepatitis C virus (HCV) is a major cause of liver disease and a potential cause of substantial morbidity and mortality worldwide. The overall prevalence of HCV infection is 2%, representing 120 million people worldwide. Current standard treatment using pegylated interferon and ribavirin is effective in only 50% of the patients infected with HCV genotype 1, and is associated with significant side effects. Therefore, it is still of importance to develop new drugs for treatment of HCV. Antiviral substances obtained from natural products, including medicinal plants, are potentially good targets to study. In this study, we evaluated Indonesian medicinal plants for their anti-HCV activities.Methods: Ethanol extracts of 21 samples derived from 17 species of medicinal plants explored in the East Java region were tested. Anti-HCV activities were determined by a cell culture method using Huh7.5 cells and HCV strains of 9 different genotypes (1a to 7a, 1b and 2b).Results: Four of the 21 samples tested showed antiviral activities against HCV: Toona sureni leaves (TSL) with 50% inhibitory concentrations (IC50) of 13.9 and 2.0 mu g/ml against the HCV J6/JFH1-P47 and -P1 strains, respectively, Melicope latifolia leaves (MLL) with IC50 of 3.5 and 2.1 mu g/ml, respectively, Melanolepis multiglandulosa stem (MMS) with IC50 of 17.1 and 6.2 mu g/ml, respectively, and Ficus fistulosa leaves (FFL) with IC50 of 15.0 and 5.7 mu g/ml, respectively. Time-of-addition experiments revealed that TSL and MLL inhibited both at the entry and post-entry steps while MMS and FFL principally at the entry step. TSL and MLL inhibited all of 11 HCV strains of all the genotypes tested to the same extent. On the other hand, FFL showed significantly weaker inhibitory activities against the HCV genotype 1a strain, and MMS against the HCV strains of genotypes 2b and 7a to a lesser extent, compared to the other HCV genotypes.Conclusions: Ethanol extracts of TSL, MLL, MMS and FFL showed antiviral activities against all the HCV genotypes tested with the exception that some genotype(s) showed significant resistance to FFL and to MMS to a lesser extent. These plant extracts may be good candidates for the development of anti-HCV drugs.

  BIOMED CENTRAL LTD, 2013年08月, VIROLOGY JOURNAL, 10, 259, 英語

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• A point mutation at Asn-534 that disrupts a conserved N-glycosylation motif of the E2 glycoprotein of hepatitis C virus markedly enhances the sensitivity to antibody neutralization

  Mikiko Sasayama, Ikuo Shoji, Myrna Adianti, Da-Peng Jiang, Lin Deng, Takafumi Saito, Hisayoshi Watanabe, Sumio Kawata, Chie Aoki, Hak Hotta

  The molecular basis of antibody neutralization against hepatitis C virus (HCV) is poorly understood. The E2 glycoprotein of HCV is critically involved in viral infectivity through specific binding to the principal virus receptor component CD81, and is targeted by anti-HCV neutralizing antibodies. A previous study showed that a mutation at position 534 (N534H) within the sixth N-glycosylation motif of E2 of the J6/JFH1 strain of HCV genotype 2a (HCV-2a) was responsible for more efficient access of E2 to CD81 so that the mutant virus could infect the target cells more efficiently. The purpose of this study was to analyze the sensitivity of the parental J6/JFH1, its cell culture-adapted variant P-47 possessing 10 amino acid mutations and recombinant viruses with the adaptive mutations to neutralization by anti-HCV antibodies in sera of HCV-infected patients. The J6/JFH1 virus was neutralized by antibodies in sera of patients infected with HCV-2a and -1b, with mean 50% neutralization titers being 1:670 and 1:200, respectively (P < 0.00001). On the other hand, the P-47 variant showed 50- to 200-times higher sensitivity to antibody neutralization than the parental J6/JFH1 without genotype specificity. The N534H mutation, and another one at position 416 (T416A) near the first N-glycosylation motif to a lesser extent, were shown to be responsible for the enhanced sensitivity to antibody neutralization. The present results suggest that the residues 534, and 416 to a lesser extent, of the E2 glycoprotein are critically involved in the HCV infectivity and antibody neutralization. J. Med. Virol. 84:229-234, 2012. (C) 2011 Wiley Periodicals, Inc.

  WILEY-BLACKWELL, 2012年02月, JOURNAL OF MEDICAL VIROLOGY, 84(2) (2), 229 - 234, 英語

  [査読有り]

  研究論文（学術雑誌）


• Generation of a recombinant reporter hepatitis C virus useful for the analyses of virus entry, intra-cellular replication and virion production

  Kazuya Kamada, Ikuo Shoji, Lin Deng, Chie Aoki, Suratno Lulut Ratnoglik, Takaji Wakita, Hak Hotta

  The lack of a culture system that efficiently produces progeny virus has hampered hepatitis C virus (HCV) research. Recently, the discovery of a novel HCV isolate JFH1 and its chimeric derivative J6/JFH1 has led to the development of an efficient virus productive culture system. To construct an easy monitoring system for the viral life cycle of HCV, we generated bicistronic luciferase reporter virus genomes based on the JFH1 and J6/JFH1 isolates, respectively. Transfection of the J6/JFH1-based reporter genome to Huh7.5 cells produced significantly greater levels of progeny virus than transfection of the JFH1 genome. Furthermore, the expression of dominant-negative Vps4, a key molecule of the endosomal sorting complex required for transport machinery, inhibited the virus production of JFH1, but not that of J6/JFH1. These results may account for the different abilities to produce progeny virus between JFH1 and J6/JFH1. Using the J6/JFH1/Luc system, we showed that the two polyanions heparin and polyvinyl sulfate decreased the infectivity of J6/JFH1/Luc virus in a dose-dependent manner. We also analyzed the function of microRNA on HCV replication and found that miR-34b could affect the replication of HCV. The reporter virus generated in this study will be useful for investigating the nature of the HCV life cycle and for identification of HCV inhibitors. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  ELSEVIER SCIENCE BV, 2012年01月, MICROBES AND INFECTION, 14(1) (1), 69 - 78, 英語

  [査読有り]

  研究論文（学術雑誌）


• Dengue virus type 2 recognizes the carbohydrate moiety of neutral glycosphingolipids in mammalian and mosquito cells（共著）

  Wichit S, Jittmittraphap A, Hidari KI, Thaisomboonsuk B, Petmitr S, Ubol S, Aoki C, Itonori S, Morita K, Suzuki T, Suzuki Y, Jampangern W

  日本細菌学会，日本ウイルス学会, 2011年02月, Microbiol Immunol., 55(2) (2), 135 - 140, 英語

  [査読有り]

  研究論文（学術雑誌）


• Dengue virus type 2 recognizes the carbohydrate moiety of neutral glycosphingolipids in mammalian and mosquito cells

  Sineewanlaya Wichit, Akanitt Jittmittraphap, Kazuya I. P. J. Hidari, Butsaya Thaisomboonsuk, Songsak Petmitr, Sukathida Ubol, Chie Aoki, Saki Itonori, Koichi Morita, Takashi Suzuki, Yasuo Suzuki, Wipawee Jampangern

  Dengue viruses infect cells by attaching to a surface receptor which remains unknown. The putative receptor molecules of dengue virus type 2 on the surface of mosquito (AP-61) and mammalian (LLC-MK2) cell lines were investigated. The immunochemical detection and structural analysis of carbohydrates demonstrated that the neutral glycosphingolipids, L-3 (GlcNAc beta 1-3Man beta 1-4Glc beta 1-1'Cer) in AP-61 cells, and nLc(4)Cer (Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer) in LLC-MK2 cells were recognized by the virus. These findings strongly suggest that neutral glycosphingolipids share the key determinant for virus binding and that the beta-GlcNAc residue may play an important role in dengue virus binding to the host cell surface.

  WILEY-BLACKWELL PUBLISHING, INC, 2011年02月, MICROBIOLOGY AND IMMUNOLOGY, 55(2) (2), 135 - 140, 英語

  [査読有り]

  研究論文（学術雑誌）


• Development of a simple system for screening anti-hepatitis C virus drugs utilizing mutants capable of vigorous replication

  Lijuan Yu, Chie Aoki, Yohko Shimizu, Kazufumi Shimizu, Wei Hou, Fumihiro Yagyu, Xianzi Wen, Masamichi Oshima, Aikichi Iwamoto, Bin Gao, Wenjun Liu, George Fu Gao, Yoshihiro Kitamura

  Replication of infectious hepatitis C virus in Huh7 cells, a human hepatocyte cell line, has become possible due to the unique properties of the JFH1 isolate. Developing reporter virus systems for a simple titration has been attempted by integrating heterologous reporter genes into the JFH1 genome, resulting in a big infectivity reduction that limits the usefulness of such reporter systems. To overcome this problem, JFH1-infected Huh7 cells were cultured continuously for 2 years to obtain Huh7-adapted JFH1 variants capable of yielding up to 1000-fold higher titers. Sequence analysis of variant genome RNA suggested that this adapted population consisted mainly of two variants. By joining the 5'-half of the obtained representative viral complementary DNA (cDNA) fragments of the variants with the 3'-half of the wildtype's, two prototype clones, A/WT and B/WT, were constructed. Replication of A/WT and B/WT viruses in Huh7 cells showed up to 100-1000-fold higher titers than the wild-type. A Renilla luciferase cDNA was inserted into the Nonstructural Protein 5A region of the A/WT and B/WT cDNA to generate A/WT-Rluc and B/WT-Rluc, respectively. Transfection of Huh7 cells with in vitro-transcribed A/WT-Rluc and B/WT-Rluc RNA resulted in production of infectious viruses with approximately 15- and 25-fold higher titers, respectively, than the wild-type RNA. The replication of A/WT-Rluc and B/WT-Rluc viruses was more vigorous than the wild-type even with insertion of the luciferase cDNA showing a good correlation of luciferase activities with infectious titers. Furthermore, interferon-alpha inhibited the replication of A/WT-Rluc and B/WT-Rluc viruses in a dose-dependent manner as determined by a luciferase assay. These results imply that our system is potentially a tool useful for screening anti-hepatitis C virus drugs in a simple and time/cost-saving manner. (C) 2010 Elsevier B.V. All rights reserved.

  ELSEVIER SCIENCE BV, 2010年11月, JOURNAL OF VIROLOGICAL METHODS, 169(2) (2), 380 - 384, 英語

  研究論文（学術雑誌）


• A recombinant replication-competent hepatitis C virus expressing Azami-Green, a bright green-emitting fluorescent protein, suitable for visualization of infected cells

  Wei Hou, Chie Aoki, Lijuan Yu, Xianzi Wen, Yinhuan Xue, Bin Gao, Wenjun Liu, George Fu Gao, Aikichi Iwamoto, Yoshihiro Kitamura

  The hepatitis C virus (HCV) production system consists of transfecting the human hepatoma cell line Huh7 with genomic HCV RNA (JFHI). To monitor HCV replication by fluorescence microscopy, we constructed a recombinant HCV clone expressing Azami-Green (mAG), a bright green fluorescent protein, by inserting the mAG gene into the nonstructural protein 5A (NS5A) genes the resultant clone was designated JFH1-hmAG. The Huh-7.5.1 (a subclone of Huh7) cells transfected with JFH1-hmAG RNA were found to produce cytoplasmic NS5A-mAG, as readily visualized by fluorescence microscopy and infectious virus, as assayed with the culture supernatant, indicating that JFH1-hmAG is infectious and replication-competent. Furthermore, the replication of this virus was inhibited by interferon alpha in a dose-dependent manner. These results suggest that JFH1-hmAG is useful for studying HCV life Cycle and the mechanism of interferon's anti-HCV action and for screening and testing new anti-HCV drugs. (C) 2008 Elsevier Inc. All rights reserved

  ACADEMIC PRESS INC ELSEVIER SCIENCE, 2008年12月, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 377(1) (1), 7 - 11, 英語

  [査読有り]

  研究論文（学術雑誌）


• Identification and characterization of carbohydrate molecules in mammalian cells recognized by dengue virus type 2

  C Aoki, KIPJ Hidari, S Itonori, A Yamada, N Takahashi, T Kasama, F Hasebe, MA Islam, K Hatano, K Matsuoka, T Taki, CT Guo, T Takahashi, Y Sakano, T Suzuki, D Miyamoto, M Sugita, D Terunuma, K Morita, Y Suzuki

  The interaction between cell surface receptors and the envelope glycoprotein (EGP) on the viral membrane surface is the initial step of Dengue virus infection. To understand the host range, tissue tropism, and virulence of this pathogen, it is critical to elucidate the molecular mechanisms of the interaction of EGP with receptor molecules. Here, using a TLC/virus-binding assay, we isolated and characterized a carbohydrate molecule on mammalian cell surfaces that is recognized by dengue virus type 2 (DEN2). Structural determination by immunochemical methods showed that the carbohydrate structure of the purified glycosphingolipid was neolactotetraosylceramide (nLc(4)Cer). This glycosphingolipid was expressed on the cell surface of susceptible cells, such as human erythroleukemia K562 and baby hamster kidney BHK-21. All serotypes of DEN viruses, DEN1 to DEN4, reacted with nLc(4)Cer, and the non-reducing terminal disaccharide residue Ga1 beta 1-4GlcNAc beta 1- was found to be a critical determinant for the binding of DEN2. Chemically synthesized derivatives carrying multiple carbohydrate residues of nLc(4), but not nLc(4) oligosaccharide, inhibited DEN2 infection of BHK-21 cells. These findings strongly suggested that multivalent nLc(4) oligosaccharide could act as a competitive inhibitor against the binding of DEN2 to the host cells.

  JAPANESE BIOCHEMICAL SOC, 2006年03月, JOURNAL OF BIOCHEMISTRY, 139(3) (3), 607 - 614, 英語

  [査読有り]

  研究論文（学術雑誌）

• 生薬センソ及びその含有成分ブファリンとガマブフォタリンのC型肝炎ウイルスとデングウイルスに対する抗ウイルス活性

  堀田博, 靭千恵, 西本幸子, 増井涼, 杉本智潮, 清水康晴, 須藤慶一, 河上仁美, 渕野裕之, 川原信夫, 川原信夫

  2022年, 甲南女子大学研究紀要2, (16) (16)


• B型肝炎ウイルスcccDNAの生成は抗腫瘍薬ミトキサントロンにより促進される

  堀田博, 堀田博, 西本幸子, とう琳, 靭千恵, 勝二郁夫, 脇田隆字, 村松正道

  2021年, 日本ウイルス学会学術集会プログラム・予稿集(Web), 68th


• アメントフラボンのB型肝炎ウイルス感染阻害活性について

  靱千恵, INDRASETIAWAN Puguh, 深野顕人, 村松正道, 堀田博, 堀田博, 亀岡正典

  2021年, 日本ウイルス学会学術集会プログラム・予稿集(Web), 68th


• Promising anti-hepatitis C virus compounds from natural resources

  Wahyuni TS, Aoki-Utsubo C, Hotta H

  2016年, Natural Product Communications, 11(8) (8), 1193 - 1200, 英語

  [査読有り][招待有り]

  記事・総説・解説・論説等（学術雑誌）


• Syntheses and Biological Assay of a Series of Lacto-N-neotetraose Cluster using Carbosilane Dendrimer Scaffolds

  Akihiro, Yamada, Ken Hatano, Koji Matsuoka, Yasuaki Esumi, Chie Aoki, Kazuya Hidari, Yasuo Suzuki, Daiyo Terunuma

  2005年, The 14th International Symposium on Organosilicon Chemistry, 134


• Isolation and characterization of glycolipids recognized with dengue virus type 2 from human and mosquito cells

  KIPJ Hidari, C Aoki, T Ogi, S Itonori, F Hasebe, K Morita, M Sugita, T Takahashi, CT Guo, D Miyamoto, T Suzuki, Y Suzuki

  OXFORD UNIV PRESS INC, 2004年11月, GLYCOBIOLOGY, 14(11) (11), 1158 - 1158, 英語

  研究発表ペーパー・要旨（国際会議）

• The multiplex CRISPR/Cas9 system efficiently suppresses HBV gene expression

  Izumi Tanaka, Risako Miki, Chie Utsubo, Masanori Kameoka

  第71回日本ウイルス学会, 2024年11月


• Butyrolactone IはB型肝炎ウイルスとC型肝炎ウイルスの感染を阻害する

  Chie Aoki-Utsubo, Dewi Triana Rizna, Muhammad Hanafi, Hak Hotta, Masanori Kameoka

  第71回日本ウイルス学会, 2024年11月


• SARS-CoV-2感染におけるサイトカインストーム誘導機構に対する脂質の関与

  梶川 美紗乃, 靱 千恵, 青野 友美, 亀岡 正典

  第70回日本ウイルス学会, 2023年11月


• 新型コロナウイルスは肝細胞でアポリポプロテインを利用して増殖する

  靱千恵, 梶原美紗乃, 青野友美, 亀岡正典

  第70回日本ウイルス学会, 2023年11月


• 新型コロナウイルスは肝細胞でアポリポプロテインBを利用して増殖する

  靱千恵, 梶川美紗乃, 青野友美, 亀岡正典

  日本薬学会第142年会, 2023年03月

  口頭発表（一般）


• 硫酸単糖型抗デングウイルス薬の合成研究(3)

  寺岡 文照, 大崎 堯裕, 靭 千恵, 左 一八, 大坪 忠宗, 池田 潔

  日本薬学会第142年会, 2023年03月


• アメントフラボンのB型肝炎ウイルス感染阻害活性について

  靱 千恵, drasetiawan Puguh, 深野 顕人, 村松 正道, 堀田 博, 亀岡 正典

  第68回日本ウイルス学会学術集会, 2021年11月, 日本語

  ポスター発表


• A biflavonoid amentoflavone inhibits hepatitis B virus infection

  Chie AOKI-UTSUBO, Indrasetiawan PUGUH, Kento FUKANO, Masamichi MURAMATSU, Masanori KAMEOKA, Hak HOTTA

  The 11th JSP-CSP-KSP Joint Symposium of Pharmacognosy, 2021年09月, 英語

  ポスター発表


• Methyl-pheophorbide A and porphyrin derivatives inhibit the viral assembly step of hepatitis C virus

  Chie Aoki-Utsubo, Masanori Kameoka, Hak Hotta

  HCV2021: The International Symposium on Hepatitis C Virus and Related Viruses, 2021年07月, 英語

  ポスター発表


• 新規デングウイルス感染阻害剤の合成（Ⅷ）

  佐藤 理貴、寺岡 文照、靭 千恵、左 一八、大坪 忠宗、池田 潔

  日本薬学会第140年会(京都), 2020年03月


• 改変型糖鎖誘導体ライブラリーによるデングウイルス感染阻害効果の検討

  靱 千恵、寺岡 文照、大坪 忠宗、池田 潔、左 一八

  日本薬学会第140年会(京都), 2020年03月


• A chlorophyll derivative, methyl-pheophorbide A inhibits hepatitis C virus assembly by affecting apolipoprotein production

  Chie Aoki-Utsubo, Hak Hotta

  第67回日本ウイルス学会学術集会, 2019年10月, 英語, 国内会議


• Antiviral Activity of Steroidal Cardiac Glycosides Obtained from Dried Toad Cake against Hepatitis C Virus

  Hak Hotta, Chie Aoki-Utsubo, Sachiko Nishimoto, Hiroyuki Fuchino, Nobuo Kawahara, Ryo Masui, Chishio Sugimoto, Yasuharu Shimizu, Keiichi Sudo

  第67回日本ウイルス学会学術集会, 2019年10月, 英語, 国内会議


• Further analysis of possible antiviral activity of CM-II-sPLA2 against HBV, HCV and HDV

  Hak Hotta, Chie Aoki-Utsubo, Ming Chen, Sachiko Nishimoto, Lin Deng, Yohei Miyayama, Makoto Hijikata, Keiko Shindo, Takeshi Noda, Michinori Kohara, Senko Tsukuda, Koichi Watashi, Takaji Wakita

  HBV2019 (International HBV Meeting), 2019年10月, 英語, 国際会議


• Potent Anti-HCV Activity of Bufalin and Gamabufotalin Obtained from Dried Toad Cake

  Hak Hotta, Chie Aoki-Utsubo, Sachiko Nishimoto, Hiroyuki Fuchino, Nobuo Kawahara, Ryo Masui, Chishio Sugimoto, Yasuharu Shimizu, Keiichi Sudo

  International Meeting on HCV and Related Viruses 2019, 2019年10月, 英語, 国際会議


• インドネシア原産薬用植物の抗B型肝炎ウイルス活性について

  靱千恵, Puguh Indrasetiawan, Yan Mardiani, Muhammad Hanafi, Sri Hartati, Tutik Sri Wahyuni, 亀岡正典, 矢野嘉彦, 堀田博, 林祥剛

  日本生薬学会第66年会, 2019年09月, 日本語, 国内会議


• Methyl-pheophorbide AによるC型肝炎ウイルス感染性粒子形成阻害機構の解析

  靱千恵, 堀田博

  第139年回 日本薬学会, 2019年03月, 日本語, 国内会議


• A crude extract from Cananga odorata exhibits antiviral activity against hepatitis B virus.

  Puguh Indrasetiawan, Chie Aoki-Utsubo, Muhammad Hanafi, Sri Hartati, Masanori Kameoka, Hak Hotta, Yoshitake Hayashi

  第139年回 日本薬学会, 2019年03月, 英語, 国内会議


• フッ素基導入型デングウイルス感染阻害剤の合成

  向原大貴, 寺岡文照, 靱千恵, 左一八, 大坪忠宗, 池田潔

  第139年会 日本薬学会, 2019年03月, 日本語, 国内会議


• 動物生薬の抗HCV活性について

  渕野裕之, 村瀬明香, 河上仁美, 川原信夫, 堀田博, 靭千恵, 増井涼, 杉本智潮, 清水康晴, 須藤慶一

  第139年会 日本薬学会, 2019年03月, 日本語, 国内会議


• Supporting evidence that the ER/ERGIC is the main budding site for the Hepatitis B virus virion

  陳明, 鄧琳, 靱千恵, 渡士幸一, 脇田隆字, 堀田博

  第63回日本ウイルス会学術集会, 2018年10月, 英語, 国内会議


• Mechanistical study of antiviral activity of snake venom sPLA2 against HBV and HCV

  Miyayama Yohei, Chen Ming, Aoki-Utsubo Chie, Deng Lin, Shido Keiko, Noda Takeshi, Kohara Michinori, Watashi Koichi, Wakita Takaji, Hijikata Makoto, Hotta Hak

  第64回日本ウイルス会学術集会, 2018年10月, 英語, 国内会議


• Hepatitis C virus infection and screening research of potential antiviral agents from natural products

  Chie Aoki-Utsubo

  International Course for Health Sciences Summer Educational Program, 2018年09月, 英語

  公開講演，セミナー，チュートリアル，講習，講義等


• Comparative analysis of antiviral activity of sPLA2 against HBV and HCV

  Hotta H, Chen M, Aoki-Utsubo C, Deng L, Miyayama Y, Hijikata M, Shido K, Noda T, Kohara M, Watashi K, Wakita T

  2018 HBV International meeting, 2018年, 英語, 国際会議


• 新規デングウイルス感染阻害剤の合成(VIII)

  寺岡文照, 左一八, 靱千恵, 大坪忠宗, 池田潔

  日本薬学会第138年会, 2018年, 日本語, 国内会議


• 化合物ライブラリーを用いた抗デングウイルス活性を示す化合物の探索

  上野稔, 靱千恵, 小瀧将裕, 亀岡正典

  第25回トガ•フラビ•ペスチウイルス研究会, 2018年, 日本語, 国内会議

  口頭発表（一般）


• 含フッ素デングウイルス感染阻害剤の合成研究

  寺岡文照, 向原大貴, 左一八, 靱千恵, 大坪忠宗, 池田潔

  第57回日本薬学会中国四国支部第学術大会, 2018年, 日本語, 国内会議

  口頭発表（一般）


• Chlorophyll-breakdown product, methyl-pheophorbide A inhibits hepatitis C virus infection by suppressing virus assembly

  靱千恵, Muhammad Hanafi, Pratiwi Sudarmono, 清水洋子, 堀田博

  第63回日本ウイルス会学術集会, 2017年10月, 英語, 国内会議

  ポスター発表


• Dryobalanops aromatica 葉部からのオリゴスチルベノイド、vaticanol B は C 型 肝炎ウイルスの感染を阻害する

  靭千恵, Hanafi M, Widyamawaruyanti A, Armanti TD, 渕野裕之, 川原信夫, Sudarmono P, 堀田博

  日本薬学会第137年会, 2017年03月, 日本語, 仙台, 国内会議

  ポスター発表


• Supporting evidence that the ER/ERGIC is the main budding site for the Hepatitis B virus virion

  Chen M, Deng L, Aoki-U C, Watashi K, Wakita T, Hotta H

  2017 HBV International meeting, 2017年, 英語, 国際会議


• Broad-spectrum Antiviral Phospholipase A2 (PLA2) That Targets the Viral Envelope Lipid Bilayer derived from the ER/ERGIC Membranes

  Hotta H, Chen M, Aoki-U C, Deng L, Miyayama Y, Hijikata M, Shido K, Noda T, Kohara M, Watashi K, Wakita T

  24th International Symposium on Hepatitis C Virus and Related Viruses, 2017年, 英語, 国際会議


• Antiviral activities of the scorpine-like peptide Smp 76 isolated from Scorpio maurus palmatus against dengue virus and hapatitis C virus.

  Hotta H, El-Bitar AA, Sarhan MM, Rahman MA, Possani LD, Chen M, Deng L, Aoki-Utsubo C

  23th International Symposium on Hepatitis C Virus and Related Viruses, 2016年10月, 英語, Kyoto, 国際会議

  ポスター発表


• Cholesterol-lowering statins enhance HCV virion release from infected cells through activation of ERK5

  Chie Aoki, Muhamma Hanafi, Leonardus B.S. Kardono, Beti Dewi, Pratiwi Sudarmono, Yohko Shimizu, Takaji Wakita, Hak Hotta

  22th International Symposium on Hepatitis C Virus and Related Viruses, 2015年10月, 英語, 国際会議

  ポスター発表


• Lovastatin enhances HCV virion release through activation of ERK5.

  Chie Aoki, Muhammad Hanafi, Leonardus Kardono, Pratiwi Sudarmono, Yohko Shimizu, Takaji Wakita, Hak Hotta

  第63回日本ウイルス会学術集会, 2015年10月, 英語, 国内会議

  口頭発表（一般）


• Inhibition of hepatitis C virus replication by Chalepin and Pseudane IX isolated from Ruta angustifolia leaves.

  Wahyuni TS, Widyawaruyanti A, Lusida MI, Fuad A, Soetjipto, Fuchino H, Kawahara N, Hayashi Y, Aoki C, Hotta H

  日本薬学会第135年会, 2015年03月, 英語, 日本薬学会, 神戸, 国内会議

  口頭発表（一般）


• Aspergillus terreus からの精製物質ロバスタチンはC型肝炎ウイルス感染性粒子放出を促進する.

  青木千恵, Muhanmad Hanafi, Leonardus B.S. Kardono, 清水洋子, Pratiwi Sudarmono, 堀田博

  日本薬学会第135年会, 2015年03月, 日本語, 日本薬学会, 神戸, 国内会議

  口頭発表（一般）


• C型肝炎ウイルス感染によるTGF-βスーパーファミリーにおけるSmad2/3とSmad1/5/9経路の脱制御とその分子機序の解明.

  松岡陽子, Deng Lin, 朝日朱美, 青木千恵, 勝二郁夫, 堀田博

  第62回日本ウイルス学会学術集会., 2014年11月, 日本語, 日本ウイルス学会, 横浜, 国内会議

  口頭発表（一般）


• Aspergillus terreus 抽出液及びその精製物ロバスタチンは高濃度でC型肝炎ウイルス感染性粒子の放出を促進する.

  青木千恵, Muhanmad Hanafi, Leonardus B.S. Kardono, 清水洋子, Pratiwi Sudarmono, 堀田博

  第67回日本細菌学会関西支部総会学術集会, 2014年11月, 日本語, 日本細菌学会関西支部, 西宮, 国内会議

  口頭発表（一般）


• HCV dysregulates Smad2/3- and Smad1/5-signaling pathways of the TGF-β superfamily.

  Yoko Matsuoka, Lin Deng, Akemi Asahi, Chie Aoki, Ikuo Shoji, Hak Hotta

  21th International Symposium on Hepatitis C Virus and Related Viruses., 2014年09月, 英語, Organising Committee of the 21th International Symposium on Hepatitis C Virus and Related Viruses, Banff, Banff, 国際会議

  ポスター発表


• Chalepin and pseudane IX isolated from Ruta angustifolia leaves inhibit hepatitis C virus replication.

  Wahyuni TS, Widyawaruyanti A, Lusida MI, Fuad A, Soetjipto, Fuchino H, Kawahara N, Hayashi Y, Aoki C, Hotta H

  The 13th Awaji International Forum on Infection and Immunity in Nara., 2014年09月, 英語, The Awaji International Forum on Infection and Immunity, Nara, 国際会議

  ポスター発表


• Chlorophill分解産物Pheophorbide a、Chlorin e6及び半合成誘導体Mono-L-aspartyl chlorin e6 (NPe6) はC型肝炎ウイルス増殖を阻害する

  Suratno Lulut Ratnoglik, 青木千恵, 河本真理, Pratiwi Sudarmono, Lin Deng, 勝二郁夫, 渕野裕之, 川原信夫, 堀田博

  第61回日本ウイルス学会学術集会, 2013年11月, 日本語, 日本ウイルス学会, 神戸, 国内会議

  ポスター発表


• Aspergillus terreus 抽出液及びそれに含まれるロバスタチンは高濃度でC型肝炎ウイルス感染性粒子産生を促進する

  青木千恵, 清水洋子, Sudarmono Pratiwi, Muhanmad Hanafi, Kardono B.S. Leonardus, 堀田博

  第61回日本ウイルス学会学術集会, 2013年11月, 日本語, 日本ウイルス学会, 神戸, 国内会議

  口頭発表（一般）


• Various statins at high concentrations enhance HCV virion release from the infected cells

  Chie Aoki, Sri Hartati, Muhanmad Hanafi, Leonardus B.S. Kardono, Tjahjani Mirawati Sudiro, Beti Ernawati Dewi, Pratiwi Sudarmono, Yoko Shimizu, Hak Hotta

  20th International Symposium on Hepatitis C Virus and Related Viruses., 2013年10月, 英語, Organising Committee of the20th International Symposium on Hepatitis C Virus and Related Viruses, Melbourne, Australia, 国際会議

  ポスター発表


• Development of a prophylactic and therapeutic vaccine against Hepatitis C virus

  Suratno Lulut Ratnoglik, Dapeng Jiang, Chie Aoki, Pratiwi Sudarmono, Lin Deng, Ikuo Shoji, Hak Hotta

  20th International Symposium on Hepatitis C Virus and Related Viruses., 2013年10月, 英語, Organising Committee of the20th International Symposium on Hepatitis C Virus and Related Viruses, Melbourne, Australia, 国際会議

  ポスター発表


• Antiviral activity of chlorophyll derivatives, pheophorbide a, chlorin e6 and mono-L-aspartyl chlorin e6 (NPe6), against hepatitis C virus

  Hak Hotta, Chie Aoki, Suratno Lulut Ratnoglik, Pratiwi Sudarmono, Mari Komoto, Lin Deng, Ikuo Shoji, Hiroyuki Fuchino, Nobuo Kawahara

  20th International Symposium on Hepatitis C Virus and Related Viruses., 2013年10月, 英語, Organising Committee of the20th International Symposium on Hepatitis C Virus and Related Viruses, Melbourne, Australia, 国際会議

  ポスター発表


• 抗HCV活性を有する薬用植物の探索

  渕野裕之, 大根谷章浩, 宮永賢, 青木千恵, Suratno Lulut Ratnoglik, 堀田博, 川原信夫

  日本生薬学会第60回年会, 2013年09月, 日本語, 日本生薬学会, 札幌, 国内会議

  ポスター発表


• Antiviral Activity of Indonesian Plants from East Java Region Againts Hepatitis C Virus.

  Wahyuni Tutik Sri, Tumewu Lydia, Permatasari Adita Ayu, Apriani Evhy, Adianti Myrna, Rahman Abdul, Widyawaruyanti Aty, Lusida Maria Inge, Fuad Achamd, Soetjipto, Aoki Chie, Fuchino Hiroyuki, Kawahara Nobuo, Hotta Hak

  International Conference on Natural Products, 2013年03月, 英語, Organising Committee of the International Conference on Natural ProductsViruses, Shah Alam, Malaysia., Hepatitis C virus (HCV) is a major cause of liver disease worldwide and a potential cause of substantial morbidity and mortality in the future. The most recent WHO estimate of the prevalence of HCV infection is 2%, representing 120 million people. Current standard of care is effective in only 50% of the patients, poorly tolerated, and associated with significant side effects an, 国際会議

  口頭発表（一般）


• C型肝炎ウイルスに対する予防および治療ワクチン開発に関する研究

  姜大鵬, Ratnoglik Lulut, Suratno, 青木千恵, Lin Deng, 勝二郁夫, 堀田博

  第60回日本ウイルス学会学術集会, 2012年11月, 日本語, 日本ウイルス学会, 大阪, 【目的と意義】Ｃ型肝炎ウイルス（HCV）慢性感染者は、日本で約200万人、全世界で約1億7,000万～2億人と推定されている。最近認可されたより治療効果の高い三者併用療法でも、30%近い症例で完全治癒が望めず、HCV 治療ワクチンと新たな感染者発生を防止する予防ワクチンの開発が強く求められている。我々は、HCVに対する予防ワクチンと治療ワクチンを開発する目的で、HCVのエンベロープタンパク質及び非構造タンパク質の一部をコードする遺伝子領域を組み込んだ発現プラスミドを数種類作製し、DNAワクチンとしてマウスに接種して、中和抗体産生及び細胞性免疫誘導を検討した。【材料と方法】1）DNAワクチン：HCV(1b型)のエンベロープタンパク質(E2)及び非構造タンパク質の一部(NS3)をコードする遺伝子領域を組み込んだ発現プラスミドを数種類作製した。2）マウス免, 国内会議

  口頭発表（一般）


• Development of therapeutic and preventive vaccines against Hepatitis C virus.

  Jiang Depeng, Ratnoglik Suratno Lulut, Aoki Chie, Deng Lin, Shoji Ikuo, Hotta Hak

  19th International Symposium on Hepatitis C Virus and Related Viruses., 2012年10月, 英語, Organising Committee of the19th International Symposium on Hepatitis C Virus and Related Viruses, Venice, Italy, An estimated 170 to 200 million individuals are chronically infected with Hepatitis C virus (HCV) worldwide and 3 to 4 million individuals are newly infected each year. There is currently no vaccine available to protect against HCV. Considering the limited efficacy and high cost of treatment for chronic Hepatitis C, preventive and therapeutic vaccines against HCV are thus much, 国際会議

  ポスター発表


• Differential measurement of the number of plus- and minus- RNA molecules of hepatitis C virus in infected cells.

  Yagyu F, Aoki C, Yu L, Iwamoto A, Kitamura Y

  17th International Symposium on Hepatitis C Virus and Related Viruses, 2010年10月, 英語, 国際会議


• Variants of hepatitis C virus JFH-1 strain adapted to Huh7 cells.

  Yu L, Aoki C, Shimizu Y, Shimizu K, Yagyu F, Hou W, Oshima M, Iwamoto A, Gao B, Liu FW, Gao GF, Kitamura Y

  17th International symposium on hepatitis C virus and related viruses, 2010年09月, 英語, Organising Committee of the17th International Meeting on Hepatitis C Virus and Related Viruses, Yokohama, Japan, 国際会議

  ポスター発表


• Differential measurement of the number of plus- and minus- RNA molecules of hepatitis C virus in infected cells

  Yagyu F, Aoki C, Yu L, Iwamoto A, Kitamura Y

  17th International symposium on hepatitis C virus and related viruses, 2010年09月, 英語, Organising Committee of the17th International Meeting on Hepatitis C Virus and Related Viruses, Yokohama, Japan, 国際会議

  ポスター発表


• Hepatitis C Virus Replicon with Gaussia Luciferase.

  Aoki C, Yagyu F, Shimizu Y, Shimizu K, Oshima M, Iwamoto A, Kitamura Y

  16th International Symposium on Hepatitis C Virus and Related Viruses, 2009年10月, 英語, 国際会議


• Interferon-Induced Protein 44 (IFI44)に関する研究

  青木千恵, 清水洋子, 清水一史, 大島正道, 岩本愛吉, 北村義浩

  2009年10月, 日本語, 国内会議


• Anti-HCV activity of interferon-inducible proteins, IFI44/IFI44L.

  Aoki C, Yu L, Shimizu Y, Shimizu K, Oshima M, Liu W, Gao GF, Iwamoto A, Kitamura Y

  The 15th International Symposium on Hepatitis C Virus and Related Viruses, 2008年06月, 英語, 国際会議

  口頭発表（一般）


• Hepatitis C virus replication in cultured mammalian cells.

  Aoki C

  International Symposium on Basic and Applied Immunology, 2007年, 国際会議


• デングウイルスエンベロープタンパク質と宿主由来糖鎖分子との相互作用の解析および糖鎖誘導体によるデングウイルス感染阻害効果の検討

  青木千恵, 左一八, 森田公一, 長谷部太, 高橋忠信, 鈴木隆, 鈴木康夫

  第53回日本ウイルス学会学術集会, 2005年10月, 日本語, 国内会議

  口頭発表（一般）


• デング熱ウイルス結合性糖鎖分子の構造及びその性状解析

  青木千恵, 左一八, 森田公一, 長谷部太, 宮本大誠, 鈴木隆, 鈴木康夫

  第52回日本ウイルス学会学術集会, 2004年10月, 日本語, 国内会議


• Isolation and characterization Isolation and characterization of carbohydrate molecules recognized with dengue virus from human and mosquito cells.

  Aoki C, Hidari KI, Iwai K, Suzuki T, Miyamoto D, Morita K, Suzuki Y

  Pharmaceutical Sciences World Congress, 2004年, 国際会議


• デング熱ウイルス結合性糖鎖分子の構造およびその性状解析

  青木千恵, 左一八, 森田公一, 長谷部太, 宮本大誠, 鈴木隆, 鈴木康夫

  第123回日本薬学会, 2003年03月, 日本語, 国内会議

  ポスター発表

• 日本生薬学会


• 日本薬学会


• 日本ウイルス学会

• 新型コロナウイルス感染増殖における脂質代謝系の役割の解明

  靭千恵

  木下基礎科学研究基金助成事業, 2021年08月 - 2023年03月, 研究代表者


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  靭 千恵

  日本学術振興会, 二国間交流事業, 2018年04月 - 2021年03月, 研究代表者

  競争的資金


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  靭 千恵

  稲盛財団助成研究, 2018年04月 - 2019年09月, 研究代表者

  競争的資金


• インドネシアにおける肝疾患の早期診断治療への教育システムの確立

  林 祥剛

  科学研究費補助金／基盤研究(B), 2016年04月 - 2019年03月

  競争的資金