scholarly journals Antiviral effect of Archidendron pauciflorum leaves extract to hepatitis C virus: An in vitro study in JFH-1 strain

2018 ◽  
Vol 27 (1) ◽  
pp. 12-8 ◽  
Author(s):  
Sri Hartati ◽  
Chie Aoki ◽  
Muhammad Hanafi ◽  
Marissa Angelina ◽  
Pratiwi Soedarmono ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Entry ◽  
Methanol Extract ◽  
Antiviral Drug ◽  
Antiviral Effect ◽  
Hcv Genotype ◽  
Butanol Fraction ◽  
Post Entry

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.

scholarly journals Screening and Rational Design of Hepatitis C Virus Entry Inhibitory Peptides Derived from GB Virus A NS5A

2012 ◽  
Vol 87 (3) ◽  
pp. 1649-1657 ◽  
Author(s):  
Xiuying Liu ◽  
Yibing Huang ◽  
Min Cheng ◽  
Ling Pan ◽  
Youhui Si ◽  
...  
Keyword(s):  
Cell Culture ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Entry ◽  
Rational Design ◽  
Antiviral Drug ◽  
Inhibitory Effect ◽  
Content Type ◽  
Peptide Helicity

ABSTRACTChronic infection by hepatitis C virus (HCV) is a cause of the global burden of liver diseases. HCV entry into hepatocytes is a complicated and multistep process that represents a promising target for antiviral intervention. The recently reported amphipathic α-helical virucidal peptide (C5A) from the HCV NS5A protein suggests a new category of antiviral drug candidates. In this study, to identify C5A-like HCV inhibitors, synthetic peptides derived from the C5A-corresponding NS5 protein region of selectedFlaviviridaeviruses were evaluated for their anti-HCV activities. A peptide from GB virus A (GBV-A), but not other flaviviruses, demonstrated an inhibitory effect on HCV infection. Through a series of sequence optimizations and modifications of the peptide helicity and hydrophobicity, we obtained a peptide designated GBVA10-9 with highly potent anti-HCV activity. GBVA10-9 suppressed infection with both cell culture-derived and pseudotyped HCVin vitro, and the 50% cell culture inhibitory concentration ranged from 20 nM to 160 nM, depending on the genotypic origin of the envelope proteins. GBVA10-9 had no detectable effects on either HCV attachment to Huh7.5.1 cells or viral RNA replication. No virucidal activity was found with GBVA10-9, suggesting an action mechanism distinct from that of C5A. The inhibitory effect of GBVA10-9 appeared to occur at the postbinding step during viral entry. Taken together, the results with GBVA10-9 demonstrated a potent activity for blocking HCV entry that might be used in combination with other antivirals directly targeting virus-encoded enzymes. Furthermore, GBVA10-9 also provides a novel tool to dissect the detailed mechanisms of HCV entry.

scholarly journals Required concentration index quantifies effective drug combinations against hepatitis C virus infection

2020 ◽  
Author(s):  
Yusuke Kakizoe ◽  
Yoshiki Koizumi ◽  
Yukino Ikoma ◽  
Hirofumi Ohashi ◽  
Takaji Wakita ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Development ◽  
Concentration Index ◽  
Rational Design ◽  
Antiviral Effect ◽  
Drug Combinations ◽  
Hcv Genotype ◽  
Clinical Drug Development ◽  
Clinical Drug

Abstract Successful clinical drug development requires rational design of combination treatments based on preclinical data. Anti-HCV drugs exhibit significant diversity in antiviral effect. Dose-response assessments can be used to determine parameters profiling the diverse antiviral effect during combination treatment. In the current study, a combined experimental and mathematical approaches were used to compare and score different combinations of anti-hepatitis C virus (HCV) treatments. A “required concentration index” was generated and used to rank the antiviral profile of possible double- and triple-drug combinations against HCV genotype 1 and 2. Rankings varied based on target HCV genotype. Interestingly, multidrug (double and triple) treatment not only augmented antiviral activity, but also reduced genotype-specific efficacy, suggesting another advantage of multidrug treatment. The current study provides a quantitative method for profiling drug combinations against viral genotypes, to better inform clinical drug development.

scholarly journals Nonhepatic Cell Lines HeLa and 293 Support Efficient Replication of the Hepatitis C Virus Genotype 2a Subgenomic Replicon

2005 ◽  
Vol 79 (1) ◽  
pp. 592-596 ◽  
Author(s):  
Takanobu Kato ◽  
Tomoko Date ◽  
Michiko Miyamoto ◽  
Zijiang Zhao ◽  
Masashi Mizokami ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Sequencing ◽  
Cell Lines ◽  
Sequencing Analysis ◽  
Virus Genotype ◽  
Subgenomic Replicon ◽  
Hcv Genotype ◽  
Efficient Replication

ABSTRACT The hepatitis C virus (HCV) genotype 2a subgenomic replicon can replicate in two human non-hepatocyte-derived cell lines, HeLa and 293, with in vitro-transcribed replicon RNA. Sequencing analysis revealed that mutations in HCV-derived regions were not essential for replication in these cells, as some clones displayed no mutations.

scholarly journals Required concentration index quantifies effective drug combinations against hepatitis C virus infection

2020 ◽  
Author(s):  
Yusuke Kakizoe ◽  
Yoshiki Koizumi ◽  
Yukino Ikoma ◽  
Hirofumi Ohashi ◽  
Takaji Wakita ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Development ◽  
Concentration Index ◽  
Rational Design ◽  
Antiviral Effect ◽  
Drug Combinations ◽  
Hcv Genotype ◽  
Clinical Drug Development ◽  
Clinical Drug

Abstract Successful clinical drug development requires rational design of combination treatments based on preclinical data. Anti-HCV drugs exhibit significant diversity in antiviral effect. Dose-response assessments can be used to determine parameters profiling the diverse antiviral effect during combination treatment. In the current study, a combined experimental and mathematical approaches were used to compare and score different combinations of anti-hepatitis C virus (HCV) treatments. A “required concentration index” was generated and used to rank the antiviral profile of possible double- and triple-drug combinations against HCV genotype 1b and 2a. Rankings varied based on target HCV genotype. Interestingly, multidrug (double and triple) treatment not only augmented antiviral activity, but also reduced genotype-specific efficacy, suggesting another advantage of multidrug treatment. The current study provides a quantitative method for profiling drug combinations against viral genotypes, to better inform clinical drug development.

scholarly journals Persistent Hepatitis C Virus Infection In Vitro: Coevolution of Virus andHost

2006 ◽  
Vol 80 (22) ◽  
pp. 11082-11093 ◽  
Author(s):  
Jin Zhong ◽  
Pablo Gastaminza ◽  
Josan Chung ◽  
Zania Stamataki ◽  
Masanori Isogawa ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Entry ◽  
Hcv Infection ◽  
Accelerated Expansion ◽  
Adaptive Mutation ◽  
Hcv Rna ◽  
Sequencing Analysis ◽  
Selection Of

ABSTRACT The virological and cellular consequences of persistent hepatitis C virus (HCV) infection have been elusive due to the absence of the requisite experimental systems. Here, we report the establishment and the characteristics of persistent in vitro infection of human hepatoma-derived cells by a recently described HCV genotype 2a infectious molecular clone. Persistent in vitro infection was characterized by the selection of viral variants that displayed accelerated expansion kinetics, higher peak titers, and increased buoyant densities. Sequencing analysis revealed the selection of a single adaptive mutation in the HCV E2 envelope protein that was largely responsible for the variant phenotype. In parallel, as the virus became more aggressive, cells that were resistant to infection emerged, displaying escape mechanisms operative at the level of viral entry, HCV RNA replication, or both. Collectively, these results reveal the existence of coevolutionary events during persistent HCV infection that favor survival of both virus and host.

scholarly journals Identification and Tracking of Antiviral Drug Combinations

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1178 ◽  
Author(s):  
Aleksandr Ianevski ◽  
Rouan Yao ◽  
Svetlana Biza ◽  
Eva Zusinaite ◽  
Andres Mannik ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Human Lung ◽  
Antiviral Drug ◽  
A549 Cells ◽  
Drug Combinations ◽  
Synergistic Activity ◽  
Lung Epithelial ◽  
Hiv 1

Combination therapies have become a standard for the treatment for HIV and hepatitis C virus (HCV) infections. They are advantageous over monotherapies due to better efficacy, reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections. Here, we identify new synergistic combinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), echovirus 1 (EV1), hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1) in vitro. We observed synergistic activity of nelfinavir with convalescent serum and with purified neutralizing antibody 23G7 against SARS-CoV-2 in human lung epithelial Calu-3 cells. We also demonstrated synergistic activity of nelfinavir with EIDD-2801 or remdesivir in Calu-3 cells. In addition, we showed synergistic activity of vemurafenib with emetine, homoharringtonine, anisomycin, or cycloheximide against EV1 infection in human lung epithelial A549 cells. We also found that combinations of sofosbuvir with brequinar or niclosamide are synergistic against HCV infection in hepatocyte-derived Huh-7.5 cells, and that combinations of monensin with lamivudine or tenofovir are synergistic against HIV-1 infection in human cervical TZM-bl cells. These results indicate that synergy is achieved when a virus-directed antiviral is combined with another virus- or host-directed agent. Finally, we present an online resource that summarizes novel and known antiviral drug combinations and their developmental status.

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