No p7 inhibitor has yet been de?nitively proven to be...

No p7 inhibitor has yet been de?nitively proven to be effectiveagainst HCV
in vivo
. So far, clinical data is available for amantadinewhere results have been variable, some trials showing a sus-tained virological response in previous interferon non-responders,althoughtheneteffectwasnotstatisticallysigni?cant(Deltenreetal., 2004).In this regard, it is noteworthy that the ability of aman-tadine to inhibit HCV p7 ion channels and HCV replication
in vitro
appearstobehighlydependentontheviralgenotypeandsequenceof the p7 isolate (Haqshenas et al., 2007; Steinmann et al., 2007b;Grif?n et al., 2008).A phase II trial of the imminosugar UT-231Bfailed to demonstrate any antiviral ef?cacy in genotype 1, inter-feron non-responder HCV-infected subjects (United Therapeuticscompany website, clinical trial identi?er NCT00069511).In summary, BIT225 represents the ?rst molecule of a newclass of compounds with antiviral activity against HCV and relatedviruses:substitutednapthoylguanidines.Theprobablemechanismof action of BIT225 is via inhibition of p7 ion channel activity,though this remains to be de?nitively proven. The strong syn-ergybetweenBIT225,rIFN
?
andribavirinbodeswellforthefuturedevelopmentofBIT225,orrelatedanalogues,incombinationther-apies for HCV treatment