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Article: [Mechanisms of hepatitis B virus replication].

Hotta, Hak

Nihon rinsho. Japanese journal of clinical medicine

2015 Volume 73 Suppl 9, Page(s) 366–371

MeSH term(s)	Genome, Viral ; Hepatitis B/virology ; Hepatitis B virus/genetics ; Hepatitis B virus/physiology ; Humans ; Life Cycle Stages ; Virion ; Virus Replication
Language	Japanese
Publishing date	2015-12
Publishing country	Japan
Document type	Journal Article
ZDB-ID	390903-7
ISSN	0047-1852
ISSN	0047-1852
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Potent virucidal activity of honeybee "Apis mellifera" venom against Hepatitis C Virus.

Sarhan, Moustafa / El-Bitar, Alaa M H / Hotta, Hak

Toxicon : official journal of the International Society on Toxinology

2020 Volume 188, Page(s) 55–64

Abstract: Hepatitis C virus (HCV) is a global viral widespread without an available vaccine to prevent infection. HCV infection can cause serious liver diseases such as hepatocellular carcinoma (HCC). Current treatment of HCV infection depends on the FDA approved ... ...

Abstract	Hepatitis C virus (HCV) is a global viral widespread without an available vaccine to prevent infection. HCV infection can cause serious liver diseases such as hepatocellular carcinoma (HCC). Current treatment of HCV infection depends on the FDA approved direct-acting antivirals (DAAs) which have side effects and expensive. Thus, development of a novel, more efficient, along with affordable pricing anti-HCV agents is still required. The purpose of the present study is to evaluate the antiviral effects of bee venom (BV) from the honeybee Apis mellifera on the HCV replication life cycle. The crude venom and its components were examined for their anti-HCV activities using Huh7it-1 cultured cells and the JFH1 strain of HCV genotype 2a. Results revealed that BV inhibited HCV infection with 50% inhibitory concentration (IC
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Bee Venoms/pharmacology ; Bees ; Carcinoma, Hepatocellular ; Cell Line ; Hepacivirus ; Hepatitis C ; Hepatitis C, Chronic ; Liver Neoplasms ; Melitten ; Peptides
Chemical Substances	Antiviral Agents ; Bee Venoms ; Peptides ; Melitten (20449-79-0) ; mast cell degranulating peptide (32908-73-9)
Language	English
Publishing date	2020-10-14
Publishing country	England
Document type	Journal Article
ZDB-ID	204479-1
ISSN	1879-3150 ; 0041-0101
ISSN (online)	1879-3150
ISSN	0041-0101
DOI	10.1016/j.toxicon.2020.10.014
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A study on the relationship between HCV NS3 and endogenous IRF-3

Hong-Ping Liang / Hotta Hak / Jian-Min Ji

European Journal of Inflammation, Vol

2018 Volume 16

Abstract: This study aims to investigate the relationship between hepatitis C virus (HCV) NS3/4A and endogenous interferon regulatory factor-3 (IRF-3). The localization of endogenous IRF-3 protein before and after virus infection was analyzed by immunofluorescence ...

Abstract	This study aims to investigate the relationship between hepatitis C virus (HCV) NS3/4A and endogenous interferon regulatory factor-3 (IRF-3). The localization of endogenous IRF-3 protein before and after virus infection was analyzed by immunofluorescence assay (IFA). IFA results revealed that the synergistic action of transfection and HCV virus infection could more effectively reduce the nuclear translocation of endogenous IRF-3 in HeLa cells, compared to the activation of Sendai virus infection alone. The highest nuclear translocation of endogenous IRF-3 in transfected HeLa cells occurred at 24 h after Sendai virus infection. Our study was consistent with a published paper, which revealed that HCV NS3/4A protease could suppress the activation of IRF-3 and was indispensable in the transcription of interferon (IFN)-α/β.
Keywords	Medicine ; R
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Amentoflavone inhibits hepatitis B virus infection via the suppression of preS1 binding to host cells.

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

Microbiology and immunology

2023 Volume 67, Issue 6, Page(s) 281–292

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Hepatitis B virus ; Biflavonoids/pharmacology ; Biflavonoids/metabolism ; Biflavonoids/therapeutic use ; Hepatitis B/drug therapy ; Hepatocytes ; Antiviral Agents/therapeutic use ; Virus Internalization
Chemical Substances	amentoflavone (9I1VC79L77) ; Biflavonoids ; Antiviral Agents
Language	English
Publishing date	2023-04-04
Publishing country	Australia
Document type	Journal Article
ZDB-ID	224792-6
ISSN	1348-0421 ; 0385-5600
ISSN (online)	1348-0421
ISSN	0385-5600
DOI	10.1111/1348-0421.13064
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Promising Anti-Hepatitis C Virus Compounds from Natural Resources.

Wahyuni, Tutik Sri / Utsubo, Chie Aoki / Hotta, Hak

Natural product communications

2019 Volume 11, Issue 8, Page(s) 1193–1200

Abstract: Hepatitis C virus (HCV) infection is a major worldwide problem, which involves approximately 170 million people. High morbidity of patients is caused by chronic infection, which leads to liver cirrhosis, hepatocellular carcinoma and other HCV-related ... ...

Abstract	Hepatitis C virus (HCV) infection is a major worldwide problem, which involves approximately 170 million people. High morbidity of patients is caused by chronic infection, which leads to liver cirrhosis, hepatocellular carcinoma and other HCV-related diseases. The sustained virological response (SVR) has been markedly improved to be >90% by the current standard interferon (IFN)-free treatment regimens with a combination of direct-acting antiviral agents (DAAs) targeting the viral NS3 protease, NS5A multi-function protein and NS5B RNA-dependent RNA polymerase, compared with 50-70% of SVR rates achieved by the previous standard IFN-based treatment regimens with or without an NS3 protease inhibitor. However, the emergence of DAA-resistant HCV strains and the limited access to the DAAs due to their high cost could be major concerns. Also, the long-term prognosis of patients treated with DAAs, such as the possible development of hepatocellular carcinoma, still needs to be further evaluated. Natural resources are considered to be good candidates to develop anti-HCV agents. Here, we summarize anti-HCV compounds obtained from natural resources, including medicinal plant extracts, their isolated compounds and some of their derivatives that possess high antiviral potency against HCV.
MeSH term(s)	Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Biological Products/chemistry ; Biological Products/pharmacology ; Hepacivirus/drug effects ; Hepatitis C/virology ; Humans
Chemical Substances	Antiviral Agents ; Biological Products
Language	English
Publishing date	2019-03-05
Publishing country	United States
Document type	Journal Article
ISSN	1934-578X
ISSN	1934-578X
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Virucidal activity of oriental hornet

Sarhan, Moustafa / El-Bitar, Alaa M H / Mohammadein, Amaal / Elshehaby, Mohammed / Hotta, Hak

The journal of venomous animals and toxins including tropical diseases

2021 Volume 27, Page(s) e20210039

Abstract: Background: Hepatitis C virus (HCV) infection is a major worldwide health problem that can cause liver fibrosis and hepatocellular carcinoma (HCC). The clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) that ... ...

Abstract	Background: Hepatitis C virus (HCV) infection is a major worldwide health problem that can cause liver fibrosis and hepatocellular carcinoma (HCC). The clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) that are usually expensive and have side effects. Therefore, achieving the discovery of more successful agents is always urgent. In this context, antiviral compounds that inhibit viral infections and disease progression with important therapeutic activities have been identified in animal venoms including arthropod toxins. This indicates that arthropod venoms represent a good natural source of promising candidates for new antivirals. Methods: The antiviral activity of the wasp venom (WV), isolated from the Oriental hornet ( Results: The results revealed that WV inhibited HCV infectivity with 50% inhibitory concentration (IC Conclusion: WV can inhibit the entry stage of HCV infection at non-cytotoxic concentrations. Therefore, it could be considered a potential candidate for characterization of natural anti-HCV agents targeting the entry step.
Language	English
Publishing date	2021-11-19
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2031021-3
ISSN	1678-9199
ISSN	1678-9199
DOI	10.1590/1678-9199-JVATITD-2021-0039
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Potent virucidal activity of honeybee “Apis mellifera” venom against Hepatitis C Virus

Sarhan, Moustafa / El-Bitar, Alaa M.H / Hotta, Hak

Toxicon. 2020 Dec., v. 188

2020

Abstract	Hepatitis C virus (HCV) is a global viral widespread without an available vaccine to prevent infection. HCV infection can cause serious liver diseases such as hepatocellular carcinoma (HCC). Current treatment of HCV infection depends on the FDA approved direct-acting antivirals (DAAs) which have side effects and expensive. Thus, development of a novel, more efficient, along with affordable pricing anti-HCV agents is still required. The purpose of the present study is to evaluate the antiviral effects of bee venom (BV) from the honeybee Apis mellifera on the HCV replication life cycle. The crude venom and its components were examined for their anti-HCV activities using Huh7it-1 cultured cells and the JFH1 strain of HCV genotype 2a. Results revealed that BV inhibited HCV infection with 50% inhibitory concentration (IC₅₀) of 0.05 ng/ml, while the 50% cytotoxic concentration (CC₅₀) being 20,000 ng/ml. The venom directly blocked HCV/cell entry by acting on virus particles in a dose dependent manner, whereas no interference on the host cells. Furthermore, venom showed no inhibitory effect on HCV replication and release. Interestingly, none of the main BV components including the mast cell degranulating peptide (MCD), mpamin, or the small peptides melittin (MLT) showed anti-HCV activity up to 5 μg/ml. In conclusion, these results suggest that BV has a direct virucidal activity against HCV and may exert its antiviral effect through a non-common peptide(s) or toxin complex within the crude venom. Therefore, the crude BV can be considered as a promising candidate for characterization and development of new and natural anti-HCV therapeutic agents.
Keywords	Apis mellifera ; Hepatitis C virus ; antiviral agents ; antiviral properties ; bee venoms ; cytotoxicity ; dose response ; genotype ; hepatoma ; honey bees ; inhibitory concentration 50 ; liver ; mast cells ; melittin ; peptides ; therapeutics ; toxins ; vaccines ; viruses
Language	English
Dates of publication	2020-12
Size	p. 55-64.
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	204479-1
ISSN	1879-3150 ; 0041-0101
ISSN (online)	1879-3150
ISSN	0041-0101
DOI	10.1016/j.toxicon.2020.10.014
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Virucidal and Neutralizing Activity Tests for Antiviral Substances and Antibodies.

Aoki-Utsubo, Chie / Chen, Ming / Hotta, Hak

Bio-protocol

2018 Volume 8, Issue 10, Page(s) e2855

Abstract: In a narrow definition, virucidal activity represents the activity by which to interact with and physically disrupt viral particles. In a broad definition, it includes the activity by which to functionally inhibit (neutralize) viral infectivity without ... ...

Abstract	In a narrow definition, virucidal activity represents the activity by which to interact with and physically disrupt viral particles. In a broad definition, it includes the activity by which to functionally inhibit (neutralize) viral infectivity without apparent morphological alterations of the viral particles. The viral infectivity can be measured in cell culture system by means of plaque assay, infectious focus assay, 50% tissue culture infectious dose (TCID
Language	English
Publishing date	2018-05-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2833269-6
ISSN	2331-8325 ; 2331-8325
ISSN (online)	2331-8325
ISSN	2331-8325
DOI	10.21769/BioProtoc.2855
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: 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, Chie / Chen, Ming / Hotta, Hak

Bio-protocol

2018 Volume 8, Issue 9, Page(s) e2830

Abstract: Viruses infect their host cells to produce progeny virus particles through the sequential steps of the viral life cycle, such as viral attachment, entry, penetration and post-entry events. This protocol describes time-of-addition and temperature-shift ... ...

Abstract	Viruses infect their host cells to produce progeny virus particles through the sequential steps of the viral life cycle, such as viral attachment, entry, penetration and post-entry events. This protocol describes time-of-addition and temperature-shift assays that are employed to explore which step(s) in the viral life cycle is blocked by an antiviral substance(s).
Language	English
Publishing date	2018-05-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2833269-6
ISSN	2331-8325 ; 2331-8325
ISSN (online)	2331-8325
ISSN	2331-8325
DOI	10.21769/BioProtoc.2830
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Suppression of viral RNA polymerase activity is necessary for persistent infection during the transformation of measles virus into SSPE virus.

Sakamoto, Kento / Konami, Miho / Kameda, Shinra / Satoh, Yuto / Wakimoto, Hiroshi / Kitagawa, Yoshinori / Gotoh, Bin / Jiang, Da-Peng / Hotta, Hak / Itoh, Masae

PLoS pathogens

2023 Volume 19, Issue 7, Page(s) e1011528

Abstract: Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by measles virus (MV), which typically develops 7 to 10 years after acute measles. During the incubation period, MV establishes a persistent infection in the brain and ...

Abstract	Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by measles virus (MV), which typically develops 7 to 10 years after acute measles. During the incubation period, MV establishes a persistent infection in the brain and accumulates mutations that generate neuropathogenic SSPE virus. The neuropathogenicity is closely associated with enhanced propagation mediated by cell-to-cell fusion in the brain, which is principally regulated by hyperfusogenic mutations of the viral F protein. The molecular mechanisms underlying establishment and maintenance of persistent infection are unclear because it is impractical to isolate viruses before the appearance of clinical signs. In this study, we found that the L and P proteins, components of viral RNA-dependent RNA polymerase (RdRp), of an SSPE virus Kobe-1 strain did not promote but rather attenuated viral neuropathogenicity. Viral RdRp activity corresponded to F protein expression; the suppression of RdRp activity in the Kobe-1 strain because of mutations in the L and P proteins led to restriction of the F protein level, thereby reducing cell-to-cell fusion mediated propagation in neuronal cells and decreasing neuropathogenicity. Therefore, the L and P proteins of Kobe-1 did not contribute to progression of SSPE. Three mutations in the L protein strongly suppressed RdRp activity. Recombinant MV harboring the three mutations limited viral spread in neuronal cells while preventing the release of infectious progeny particles; these changes could support persistent infection by enabling host immune escape and preventing host cell lysis. Therefore, the suppression of RdRp activity is necessary for the persistent infection of the parental MV on the way to transform into Kobe-1 SSPE virus. Because mutations in the genome of an SSPE virus reflect the process of SSPE development, mutation analysis will provide insight into the mechanisms underlying persistent infection.
MeSH term(s)	Humans ; Measles virus/genetics ; SSPE Virus/genetics ; SSPE Virus/metabolism ; Subacute Sclerosing Panencephalitis/genetics ; Subacute Sclerosing Panencephalitis/pathology ; Viral Replicase Complex Proteins/metabolism ; Persistent Infection ; Neurodegenerative Diseases ; Viral Fusion Proteins/genetics ; Viral Fusion Proteins/metabolism ; Measles/genetics ; Measles/metabolism
Chemical Substances	Viral Replicase Complex Proteins ; Viral Fusion Proteins
Language	English
Publishing date	2023-07-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011528
Database	MEDical Literature Analysis and Retrieval System OnLINE

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