Should NS5A inhibitors serve as the scaffold for all-oral anti-HCV combination therapies?

Sujit V Janardhan, Nancy S Reau Center for Liver Diseases, Section of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Chicago, Chicago, IL, USA Abstract: Chronic hepatitis C virus (HCV) infection represents a global health problem that affects up to 130–...

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Autores principales:	Janardhan SV, Reau NS
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/b87ffaa4cb8b4d57b149574f3fe3c7a4
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spelling	oai:doaj.org-article:b87ffaa4cb8b4d57b149574f3fe3c7a42021-12-02T06:08:33ZShould NS5A inhibitors serve as the scaffold for all-oral anti-HCV combination therapies?1179-1535https://doaj.org/article/b87ffaa4cb8b4d57b149574f3fe3c7a42015-04-01T00:00:00Zhttp://www.dovepress.com/should-ns5a-inhibitors-serve-as-the-scaffold-for-all-oral-anti-hcv-com-peer-reviewed-article-HMERhttps://doaj.org/toc/1179-1535Sujit V Janardhan, Nancy S Reau Center for Liver Diseases, Section of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Chicago, Chicago, IL, USA Abstract: Chronic hepatitis C virus (HCV) infection represents a global health problem that affects up to 130–150 million people worldwide. The HCV treatment landscape has been transformed recently by the introduction of direct-acting antiviral (DAA) agents that target viral proteins, including the NS3 protease, the NS5B polymerase, and the NS5A protein. Treatment with multiple DAAs in combination has been shown to result in high rates of sustained virologic response, without the need for pegylated interferon, and a shorter duration of therapy compared with interferon-based regimens; however, the optimal combination of DAAs has yet to be determined. The class of NS5A inhibitors has picomolar potency with pangenotypic activity, and recent clinical studies have shown these inhibitors to be an important component of DAA combination regimens. This review discusses the rational design of an optimal anti-HCV DAA cocktail, with a focus on the role of NS5A in the HCV life cycle, the attributes of the NS5A class of inhibitors, and the potential for NS5A inhibitors to act as a scaffold for DAA-only treatment regimens. Keywords: hepatitis C virus, NS5A, therapy, direct-acting antiviralJanardhan SVReau NSDove Medical PressarticleDiseases of the digestive system. GastroenterologyRC799-869ENHepatic Medicine: Evidence and Research, Vol 2015, Iss default, Pp 11-20 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Diseases of the digestive system. Gastroenterology RC799-869 Janardhan SV Reau NS Should NS5A inhibitors serve as the scaffold for all-oral anti-HCV combination therapies?
description	Sujit V Janardhan, Nancy S Reau Center for Liver Diseases, Section of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Chicago, Chicago, IL, USA Abstract: Chronic hepatitis C virus (HCV) infection represents a global health problem that affects up to 130–150 million people worldwide. The HCV treatment landscape has been transformed recently by the introduction of direct-acting antiviral (DAA) agents that target viral proteins, including the NS3 protease, the NS5B polymerase, and the NS5A protein. Treatment with multiple DAAs in combination has been shown to result in high rates of sustained virologic response, without the need for pegylated interferon, and a shorter duration of therapy compared with interferon-based regimens; however, the optimal combination of DAAs has yet to be determined. The class of NS5A inhibitors has picomolar potency with pangenotypic activity, and recent clinical studies have shown these inhibitors to be an important component of DAA combination regimens. This review discusses the rational design of an optimal anti-HCV DAA cocktail, with a focus on the role of NS5A in the HCV life cycle, the attributes of the NS5A class of inhibitors, and the potential for NS5A inhibitors to act as a scaffold for DAA-only treatment regimens. Keywords: hepatitis C virus, NS5A, therapy, direct-acting antiviral
format	article
author	Janardhan SV Reau NS
author_facet	Janardhan SV Reau NS
author_sort	Janardhan SV
title	Should NS5A inhibitors serve as the scaffold for all-oral anti-HCV combination therapies?
title_short	Should NS5A inhibitors serve as the scaffold for all-oral anti-HCV combination therapies?
title_full	Should NS5A inhibitors serve as the scaffold for all-oral anti-HCV combination therapies?
title_fullStr	Should NS5A inhibitors serve as the scaffold for all-oral anti-HCV combination therapies?
title_full_unstemmed	Should NS5A inhibitors serve as the scaffold for all-oral anti-HCV combination therapies?
title_sort	should ns5a inhibitors serve as the scaffold for all-oral anti-hcv combination therapies?
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/b87ffaa4cb8b4d57b149574f3fe3c7a4
work_keys_str_mv	AT janardhansv shouldns5ainhibitorsserveasthescaffoldforalloralantihcvcombinationtherapies AT reauns shouldns5ainhibitorsserveasthescaffoldforalloralantihcvcombinationtherapies
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Should NS5A inhibitors serve as the scaffold for all-oral anti-HCV combination therapies?

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