New Opportunities in Anti-Hepatitis C Virus Drug Discovery: Targeting NS4B

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Source: Antiviral Res | Posted 1 day ago

New Opportunities in Anti-Hepatitis C Virus Drug Discovery: Targeting NS4B;

Rai R, Deval J;

Antiviral Research (Feb 2011)

Current therapy for chronic hepatitis C virus (HCV) infection constitutes a

combination of pegylated interferon alfa-2a or alpha-2b and ribavirin. Although

successful for many patient populations, this regimen has numerous limitations,

including non-response, relapse, poor tolerability and long duration of

treatment. To address these shortcomings, new small molecule agents are

advancing in clinical development. Most of the current clinical candidates act

by directly inhibiting key enzymes in the viral life-cycle: the NS5B polymerase,

or the NS3/4A protease. Less well-studied, the non-structural 4B (NS4B) protein

has recently emerged as an alternative target for Direct-acting Antiviral Agents

(DAAs). NS4B is a 27-kDa membrane protein that is primarily involved in the

formation of membrane vesicles-also named membranous web-used as scaffold for

the assembly of the HCV replication complex. In addition, NS4B contains NTPase

and RNA binding activities, as well as anti-apoptotic properties. This review

summarizes the current understanding of the structure and functions of NS4B, an

essential component of the replication machinery of HCV. In this literature and

patent review, we report the recent developments in anti-NS4B drug discovery.

These advances open the possibility for future combination therapies with other

DAAs.