Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia

Atsuya Yamashita, Kazi Abdus Salam, Atsushi Furuta, Yasuyoshi Matsuda, Osamu Fujita, Hidenori Tani, Yoshihisa Fujita, Yuusuke Fujimoto, Masanori Ikeda, Nobuyuki Kato, Naoya Sakamoto, Shinya Maekawa, Nobuyuki Enomoto, Masamichi Nakakoshi, Masayoshi Tsubuki, Yuji Sekiguchi, Satoshi Tsuneda, Nobuyoshi Akimitsu, Naohiro Noda, Junichi TanakaKohji Moriishi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) is a causative agent of acute and chronic hepatitis, leading to the development of hepatic cirrhosis and hepatocellular carcinoma. We prepared extracts from 61 marine organisms and screened them by an in vitro fluorescence assay targeting the viral helicase (NS3), which plays an important role in HCV replication, to identify effective candidates for anti-HCV agents. An ethyl acetate-soluble fraction of the feather star Alloeocomatella polycladia exhibited the strongest inhibition of NS3 helicase activity, with an IC50 of 11.7 μg/mL. The extract of A. polycladia inhibited interaction between NS3 and RNA but not ATPase of NS3. Furthermore, the replication of the replicons derived from three HCV strains of genotype 1b in cultured cells was suppressed by the extract with an EC50 value of 23 to 44 μg/mL, which is similar to the IC50 value of the NS3 helicase assay. The extract did not induce interferon or inhibit cell growth. These results suggest that the unknown compound(s) included in A. polycladia can inhibit HCV replication by suppressing the helicase activity of HCV NS3. This study may present a new approach toward the development of a novel therapy for chronic hepatitis C.

Original languageEnglish
Pages (from-to)744-761
Number of pages18
JournalMarine Drugs
Volume10
Issue number4
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Feathers
Virus Replication
Hepacivirus
Inhibitory Concentration 50
Aquatic Organisms
Replicon
Chronic Hepatitis C
Chronic Hepatitis
Liver Cirrhosis
Interferons
Adenosine Triphosphatases
ethyl acetate
Hepatocellular Carcinoma
Cultured Cells
Fluorescence
Genotype
RNA
Growth

Keywords

  • Alloeocomatella polycladia
  • Hepatitis C virus
  • Marine organism
  • NS3 helicase

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia. / Yamashita, Atsuya; Salam, Kazi Abdus; Furuta, Atsushi; Matsuda, Yasuyoshi; Fujita, Osamu; Tani, Hidenori; Fujita, Yoshihisa; Fujimoto, Yuusuke; Ikeda, Masanori; Kato, Nobuyuki; Sakamoto, Naoya; Maekawa, Shinya; Enomoto, Nobuyuki; Nakakoshi, Masamichi; Tsubuki, Masayoshi; Sekiguchi, Yuji; Tsuneda, Satoshi; Akimitsu, Nobuyoshi; Noda, Naohiro; Tanaka, Junichi; Moriishi, Kohji.

In: Marine Drugs, Vol. 10, No. 4, 04.2012, p. 744-761.

Research output: Contribution to journalArticle

Yamashita, A, Salam, KA, Furuta, A, Matsuda, Y, Fujita, O, Tani, H, Fujita, Y, Fujimoto, Y, Ikeda, M, Kato, N, Sakamoto, N, Maekawa, S, Enomoto, N, Nakakoshi, M, Tsubuki, M, Sekiguchi, Y, Tsuneda, S, Akimitsu, N, Noda, N, Tanaka, J & Moriishi, K 2012, 'Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia', Marine Drugs, vol. 10, no. 4, pp. 744-761. https://doi.org/10.3390/md10040744
Yamashita, Atsuya ; Salam, Kazi Abdus ; Furuta, Atsushi ; Matsuda, Yasuyoshi ; Fujita, Osamu ; Tani, Hidenori ; Fujita, Yoshihisa ; Fujimoto, Yuusuke ; Ikeda, Masanori ; Kato, Nobuyuki ; Sakamoto, Naoya ; Maekawa, Shinya ; Enomoto, Nobuyuki ; Nakakoshi, Masamichi ; Tsubuki, Masayoshi ; Sekiguchi, Yuji ; Tsuneda, Satoshi ; Akimitsu, Nobuyoshi ; Noda, Naohiro ; Tanaka, Junichi ; Moriishi, Kohji. / Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia. In: Marine Drugs. 2012 ; Vol. 10, No. 4. pp. 744-761.
@article{a1bab2eb82e3497491fe697e4a251749,
title = "Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia",
abstract = "Hepatitis C virus (HCV) is a causative agent of acute and chronic hepatitis, leading to the development of hepatic cirrhosis and hepatocellular carcinoma. We prepared extracts from 61 marine organisms and screened them by an in vitro fluorescence assay targeting the viral helicase (NS3), which plays an important role in HCV replication, to identify effective candidates for anti-HCV agents. An ethyl acetate-soluble fraction of the feather star Alloeocomatella polycladia exhibited the strongest inhibition of NS3 helicase activity, with an IC50 of 11.7 μg/mL. The extract of A. polycladia inhibited interaction between NS3 and RNA but not ATPase of NS3. Furthermore, the replication of the replicons derived from three HCV strains of genotype 1b in cultured cells was suppressed by the extract with an EC50 value of 23 to 44 μg/mL, which is similar to the IC50 value of the NS3 helicase assay. The extract did not induce interferon or inhibit cell growth. These results suggest that the unknown compound(s) included in A. polycladia can inhibit HCV replication by suppressing the helicase activity of HCV NS3. This study may present a new approach toward the development of a novel therapy for chronic hepatitis C.",
keywords = "Alloeocomatella polycladia, Hepatitis C virus, Marine organism, NS3 helicase",
author = "Atsuya Yamashita and Salam, {Kazi Abdus} and Atsushi Furuta and Yasuyoshi Matsuda and Osamu Fujita and Hidenori Tani and Yoshihisa Fujita and Yuusuke Fujimoto and Masanori Ikeda and Nobuyuki Kato and Naoya Sakamoto and Shinya Maekawa and Nobuyuki Enomoto and Masamichi Nakakoshi and Masayoshi Tsubuki and Yuji Sekiguchi and Satoshi Tsuneda and Nobuyoshi Akimitsu and Naohiro Noda and Junichi Tanaka and Kohji Moriishi",
year = "2012",
month = "4",
doi = "10.3390/md10040744",
language = "English",
volume = "10",
pages = "744--761",
journal = "Marine Drugs",
issn = "1660-3397",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "4",

}

TY - JOUR

T1 - Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia

AU - Yamashita, Atsuya

AU - Salam, Kazi Abdus

AU - Furuta, Atsushi

AU - Matsuda, Yasuyoshi

AU - Fujita, Osamu

AU - Tani, Hidenori

AU - Fujita, Yoshihisa

AU - Fujimoto, Yuusuke

AU - Ikeda, Masanori

AU - Kato, Nobuyuki

AU - Sakamoto, Naoya

AU - Maekawa, Shinya

AU - Enomoto, Nobuyuki

AU - Nakakoshi, Masamichi

AU - Tsubuki, Masayoshi

AU - Sekiguchi, Yuji

AU - Tsuneda, Satoshi

AU - Akimitsu, Nobuyoshi

AU - Noda, Naohiro

AU - Tanaka, Junichi

AU - Moriishi, Kohji

PY - 2012/4

Y1 - 2012/4

N2 - Hepatitis C virus (HCV) is a causative agent of acute and chronic hepatitis, leading to the development of hepatic cirrhosis and hepatocellular carcinoma. We prepared extracts from 61 marine organisms and screened them by an in vitro fluorescence assay targeting the viral helicase (NS3), which plays an important role in HCV replication, to identify effective candidates for anti-HCV agents. An ethyl acetate-soluble fraction of the feather star Alloeocomatella polycladia exhibited the strongest inhibition of NS3 helicase activity, with an IC50 of 11.7 μg/mL. The extract of A. polycladia inhibited interaction between NS3 and RNA but not ATPase of NS3. Furthermore, the replication of the replicons derived from three HCV strains of genotype 1b in cultured cells was suppressed by the extract with an EC50 value of 23 to 44 μg/mL, which is similar to the IC50 value of the NS3 helicase assay. The extract did not induce interferon or inhibit cell growth. These results suggest that the unknown compound(s) included in A. polycladia can inhibit HCV replication by suppressing the helicase activity of HCV NS3. This study may present a new approach toward the development of a novel therapy for chronic hepatitis C.

AB - Hepatitis C virus (HCV) is a causative agent of acute and chronic hepatitis, leading to the development of hepatic cirrhosis and hepatocellular carcinoma. We prepared extracts from 61 marine organisms and screened them by an in vitro fluorescence assay targeting the viral helicase (NS3), which plays an important role in HCV replication, to identify effective candidates for anti-HCV agents. An ethyl acetate-soluble fraction of the feather star Alloeocomatella polycladia exhibited the strongest inhibition of NS3 helicase activity, with an IC50 of 11.7 μg/mL. The extract of A. polycladia inhibited interaction between NS3 and RNA but not ATPase of NS3. Furthermore, the replication of the replicons derived from three HCV strains of genotype 1b in cultured cells was suppressed by the extract with an EC50 value of 23 to 44 μg/mL, which is similar to the IC50 value of the NS3 helicase assay. The extract did not induce interferon or inhibit cell growth. These results suggest that the unknown compound(s) included in A. polycladia can inhibit HCV replication by suppressing the helicase activity of HCV NS3. This study may present a new approach toward the development of a novel therapy for chronic hepatitis C.

KW - Alloeocomatella polycladia

KW - Hepatitis C virus

KW - Marine organism

KW - NS3 helicase

UR - http://www.scopus.com/inward/record.url?scp=84860616119&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860616119&partnerID=8YFLogxK

U2 - 10.3390/md10040744

DO - 10.3390/md10040744

M3 - Article

C2 - 22690141

AN - SCOPUS:84860616119

VL - 10

SP - 744

EP - 761

JO - Marine Drugs

JF - Marine Drugs

SN - 1660-3397

IS - 4

ER -