Viral entry inhibition: too late for hepatitis C, but promising for other viral infections

In theory, any step of the hepatitis C virus (HCV) lifecycle can be a target for direct-acting antiviral (DAA) drugs (drugs that directly block a viral function), and/or host-targeted agents (HTA, drugs that block a cellular function essential to the viral lifecycle). Four classes of HCV DAAs and two classes of HTAs have reached late clinical development. The HCV DAAs include: inhibitors of the NS3/4A protease that block HCV polyprotein processing; inhibitors of the RNA-dependent RNA polymerase (RdRp), including nucleoside/nucleotide analogues and non-nucleoside inhibitors that block viral replication; and NS5A inhibitors that block viral replication, virion assembly and release. The HCV HTAs in development interact with cellular factors required for HCV replication; they include cyclophilin A inhibitors and microRNA-122 antagonists.1 In 2014, three drugs were approved in the European Union, including the nucleotide analogue sofosbuvir, the protease inhibitor simeprevir and the NS5A inhibitor daclatasvir. They can be...

Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Pawlotsky, J.-M. Tags: Commentary Source Type: research