scholarly journals The Hepatitis C Virus Nonstructural Protein 2 (NS2): An Up-and-Coming Antiviral Drug Target

Viruses ◽  
2010 ◽  
Vol 2 (8) ◽  
pp. 1635-1646 ◽  
Author(s):  
Ivo C. Lorenz
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Target ◽  
Nonstructural Protein ◽  
Antiviral Drug ◽  
Nonstructural Protein 2

scholarly journals Structural and Functional Studies of Nonstructural Protein 2 of the Hepatitis C Virus Reveal Its Key Role as Organizer of Virion Assembly

2010 ◽  
Vol 6 (12) ◽  
pp. e1001233 ◽  
Author(s):  
Vlastimil Jirasko ◽  
Roland Montserret ◽  
Ji Young Lee ◽  
Jérôme Gouttenoire ◽  
Darius Moradpour ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nonstructural Protein ◽  
Virion Assembly ◽  
Functional Studies ◽  
Nonstructural Protein 2

Cyclosporine A inhibits hepatitis C virus nonstructural protein 2 through cyclophilin A

Hepatology ◽  
2009 ◽  
Vol 50 (5) ◽  
pp. 1638-1645 ◽  
Author(s):  
Sandra Ciesek ◽  
Eike Steinmann ◽  
Heiner Wedemeyer ◽  
Michael P. Manns ◽  
Johann Neyts ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cyclosporine A ◽  
Nonstructural Protein ◽  
Cyclophilin A ◽  
Nonstructural Protein 2

Analysis of N-terminal processing of hepatitis C virus nonstructural protein 2.

1994 ◽  
Vol 68 (4) ◽  
pp. 2731-2734 ◽  
Author(s):  
H Mizushima ◽  
M Hijikata ◽  
Y Tanji ◽  
K Kimura ◽  
K Shimotohno
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nonstructural Protein ◽  
Nonstructural Protein 2

scholarly journals Validating Enterovirus D68-2Aproas an Antiviral Drug Target and the Discovery of Telaprevir as a Potent D68-2AproInhibitor

2019 ◽  
Vol 93 (7) ◽  
Author(s):  
Rami Musharrafieh ◽  
Chunlong Ma ◽  
Jiantao Zhang ◽  
Yanmei Hu ◽  
Jessica M. Diesing ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Enzymatic Activity ◽  
Drug Target ◽  
Treatment Options ◽  
Antiviral Drug ◽  
Peptide Sequence ◽  
Viral Pathogen ◽  
Acute Flaccid Myelitis ◽  
Enterovirus D68

ABSTRACTEnterovirus D68 (EV-D68) is a viral pathogen that leads to severe respiratory illness and has been linked with the development of acute flaccid myelitis (AFM) in children. No vaccines or antivirals are currently available for EV-D68 infection, and treatment options for hospitalized patients are limited to supportive care. Here, we report the expression of the EV-D68 2A protease (2Apro) and characterization of its enzymatic activity. Furthermore, we discovered that telaprevir, an FDA-approved drug used for the treatment of hepatitis C virus (HCV) infections, is a potent antiviral against EV-D68 by targeting the 2Aproenzyme. Using a fluorescence resonance energy transfer-based substrate cleavage assay, we showed that the purified EV-D68 2Aprohas proteolytic activity selective against a peptide sequence corresponding to the viral VP1-2A polyprotein junction. Telaprevir inhibits EV-D68 2Aprothrough a nearly irreversible, biphasic binding mechanism. In cell culture, telaprevir showed submicromolar-to-low-micromolar potency against several recently circulating neurotropic strains of EV-D68 in different human cell lines. To further confirm the antiviral drug target, serial viral passage experiments were performed to select for resistance against telaprevir. An N84T mutation near the active site of 2Aprowas identified in resistant viruses, and this mutation reduced the potency of telaprevir in both the enzymatic and cellular antiviral assays. Collectively, we report for the first time thein vitroenzymatic activity of EV-D68 2Aproand the identification of telaprevir as a potent EV-D68 2Aproinhibitor. These findings implicate EV-D68 2Aproas an antiviral drug target and highlight the repurposing potential of telaprevir to treat EV-D68 infection.IMPORTANCEA 2014 EV-D68 outbreak in the United States has been linked to the development of acute flaccid myelitis in children. Unfortunately, no treatment options against EV-D68 are currently available, and the development of effective therapeutics is urgently needed. Here, we characterize and validate a new EV-D68 drug target, the 2Apro, and identify telaprevir—an FDA-approved drug used to treat hepatitis C virus (HCV) infections—as a potent antiviral with a novel mechanism of action toward 2Apro. 2Aprofunctions as a viral protease that cleaves a peptide sequence corresponding to the VP1-2A polyprotein junction. The binding of telaprevir potently inhibits its enzymatic activity, and using drug resistance selection, we show that the potent antiviral activity of telaprevir was due to 2Aproinhibition. This is the first inhibitor to selectively target the 2Aprofrom EV-D68 and can be used as a starting point for the development of therapeutics with selective activity against EV-D68.

scholarly journals Structural and Functional Characterization of Nonstructural Protein 2 for Its Role in Hepatitis C Virus Assembly

2008 ◽  
Vol 283 (42) ◽  
pp. 28546-28562 ◽  
Author(s):  
Vlastimil Jirasko ◽  
Roland Montserret ◽  
Nicole Appel ◽  
Anne Janvier ◽  
Leah Eustachi ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Assembly ◽  
Nonstructural Protein ◽  
Functional Characterization ◽  
Nonstructural Protein 2

scholarly journals Role for TBC1D20 and Rab1 in Hepatitis C Virus Replication via Interaction with Lipid Droplet-Bound Nonstructural Protein 5A

2012 ◽  
Vol 86 (12) ◽  
pp. 6491-6502 ◽  
Author(s):  
I. Nevo-Yassaf ◽  
Y. Yaffe ◽  
M. Asher ◽  
O. Ravid ◽  
S. Eizenberg ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Replication ◽  
Lipid Droplet ◽  
Nonstructural Protein ◽  
Nonstructural Protein 5A

Mechanism of Zinc Ejection by Disulfiram in Nonstructural Protein 5A

2021 ◽  
Author(s):  
Ashfaq Ur Rehman ◽  
Guodong Zheng ◽  
Bozitao Zhong ◽  
Duan Ni ◽  
Jia-Yi Li ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nonstructural Protein ◽  
Structural Protein ◽  
Positive Strand ◽  
Positive Strand Rna ◽  
Nonstructural Protein 5A

Hepatitis C virus (HCV) is a notorious member of the enveloped, positive-strand RNA flavivirus family. Non-structural protein 5A (NS5A) plays a key role in HCV replication and assembly. NS5A is...

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