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Hepatitis C virus NS5A inhibitors and drug resistance mutations

2014; Baishideng Publishing Group; Volume: 20; Issue: 11 Linguagem: Inglês

10.3748/wjg.v20.i11.2902

2219-2840

Shingo Nakamoto, Tatsuo Kanda, Shuang Wu, Hiroshi Shirasawa, Osamu Yokosuka,

HIV/AIDS drug development and treatment

Some direct-acting antiviral agents for hepatitis C virus (HCV), such as telaprevir and boceprevir have been , such as telaprevir and boceprevir have been such as telaprevir and boceprevir have been available since 2011.It was reported that HCV NS5A is associated with interferon signaling related to HCV replication and hepatocarcinogenesis. HCV NS5A inhibi-hepatocarcinogenesis.HCV NS5A inhibi-hepatocarcinogenesis.HCV NS5A inhibitors efficiently inhibite�� ���� re�lic�tion ed HCV replication HCV replication in vitro .Human studies showed that dual, triple and quad regimens with HCV NS5A inhibitors, such as daclatasvir and ledi-, such as daclatasvir and ledi-daclatasvir and ledipasvir, in combination with other direct-acting antiviral , in combination with other direct-acting antiviral in combination with other direct-acting antiviral agents against other regions of HCV with or without peginterferon/ribavirin, could efficiently inhibit HCV , could efficiently inhibit HCV could efficiently inhibit HCV replication according to HCV genotypes.These combi-These combi-combi-n�tions �i�ht be � �o�erf�l tool for ���iffic�lt�to�tre�t�� s �i�ht be � �o�erf�l tool for ���iffic�lt�to�tre�t�� �i�ht be � �o�erf�l tool for ���iffic�lt�to�tre�t�� �����infecte�� ��tients.��irst �ener�tion�� ���� ����� �irst �ener�tion�� ���� ����� irst �ener�tion�� ���� ����� inhibitors such as daclatasvir, ledipasvir and ABT-267, which are now in phase Ⅲ clinical trials, could result in resist�nce ��t�tions.��econ�� �ener�tion�� ����� inhibi� .��econ�� �ener�tion�� ����� inhibi� ��econ�� �ener�tion�� ����� inhibitors such as GS-5816, ACH-3102, and �K-8742, have, have have displayed improvements in the genetic barrier while ments in the genetic barrier while in the genetic barrier while in the genetic barrier while maintaining potency.HCV NS5A inhibitors are safe at HCV NS5A inhibitors are safe at HCV NS5A inhibitors are safe at low concentrations, which make them attractive for use despite low genetic barriers, although, in fact, HCV HCV NS5A inhibitors should be used with HCV NS3/4A in-should be used with HCV NS3/4A in-ith HCV NS3/4A inhibitors, HCV NS5B inhibitors or peginterferon plus riba-s, HCV NS5B inhibitors or peginterferon plus riba-HCV NS5B inhibitors or peginterferon plus riba-B inhibitors or peginterferon plus riba-inhibitors or peginterferon plus riba-s or peginterferon plus riba-ribavirin.This review article describes HCV NS5A inhibitor .This review article describes HCV NS5A inhibitor This review article describes HCV NS5A inhibitor resistance mutations and recommends that HCV NS5A and recommends that HCV NS5A recommends that HCV NS5A s that HCV NS5A that HCV NS5A inhibitors be used in combination regimens potent enough to prevent the emergence of resistant variants.