Another interesting therapeutic approach is directed at host
factors important in the viral life cycle. The most promising
target are cyclophilins, a family of highly conserved cellular
peptidyl-prolyl isomerases (PPIase) involved in many cellular
processes such as protein folding and trafficking. Cyclophilin
inhibitors block the interaction of cyclophilins with HCV
proteins and hence the formation of a functional viral
replication complex. Currently, several non-immunosuppressive
cyclosporin analogs are being tested. The most potent seems to
be Alisporivir (Debio-025), tested in both HCV monoinfected
and HIV/HCV coinfected patients with promising results. The
combination of Debio 025 and PegIFN-ɑ2a showed a significant
VL reduction after 28 days in patients infected with genotypes 1,
3 and 4 (Flisiak 2009). Such host protein-targeting compounds
have the advantage of higher genetic barriers to resistance and
could be instrumental in future IFN-free regimens (Table 4.3).
factors important in the viral life cycle. The most promising
target are cyclophilins, a family of highly conserved cellular
peptidyl-prolyl isomerases (PPIase) involved in many cellular
processes such as protein folding and trafficking. Cyclophilin
inhibitors block the interaction of cyclophilins with HCV
proteins and hence the formation of a functional viral
replication complex. Currently, several non-immunosuppressive
cyclosporin analogs are being tested. The most potent seems to
be Alisporivir (Debio-025), tested in both HCV monoinfected
and HIV/HCV coinfected patients with promising results. The
combination of Debio 025 and PegIFN-ɑ2a showed a significant
VL reduction after 28 days in patients infected with genotypes 1,
3 and 4 (Flisiak 2009). Such host protein-targeting compounds
have the advantage of higher genetic barriers to resistance and
could be instrumental in future IFN-free regimens (Table 4.3).
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