Nowe lekarstwo nadchodzi, txt po angielsku

Vertex VX-950 to nowe lekarstwo, ktore akurat przeszlo juz kilka testow i ,
fachofcy zapowiadaja duze szanse w leczeniu HCV 2, 3, 4 (szkoda ze nie rzedu
1)
Niestety tekst po angielsku.



TELAPREVIR (VX-950) IS A POTENT INHIBITOR OF HCV NS3 PROTEASES DERIVED FROM
GENOTYPE NON-1 HCV-INFECTED PATIENTS

C. Lin 1, B.L. Hanzelka 1, U. Muh 1, L. Kovari 1, D.J. Bartels 1, A.M.
Tigges 1, J. Miller 1, B.G. Rao 1, A.D. Kwong 1
1 Vertex Pharmaceuticals Incorporated, Cambridge, MA, USA

Background: Telaprevir (TVR, VX-950) is a highly selective HCV NS3•4A
protease inhibitor. Strong antiviral activity, such as a continuous,
multi-log10 decline in plasma viral RNA levels, has been observed in
genotype 1 HCV-infected subjects, who received telaprevir alone (> 4-log10
reduction) or in combination with peginterferon alfa with or without
ribavirin (> 5-log10 reduction). While genotype 1 HCV accounts for the
majority of the HCV-infected population, a substantial portion of patients
are infected with genotype non-1 HCV. In this report, we evaluated in vitro
activity of telaprevir against HCV NS3•4A proteases derived from patients
infected with HCV of genotypes 2, 3, or 4.
Methods: Plasma HCV RNA was isolated from patients infected with genotypes
2, 3, or 4 HCV. A cDNA encompassing the full-length NS3 and NS4A proteins
was amplified by nested RT-PCR, cloned and sequenced. Depending on the amino
acid polymorphisms in the HCV NS3 protease domain of individual patients,
one or more clones were selected for expression and enzyme purification of
the NS3 protease domain, which was fused to the NS4A co-factor. The activity
of telaprevir against these patient-specific NS3•4A proteases was determined
in enzyme assays.
Results: The activity of telaprevir against patient isolates of genotype 2a,
2b, 3a, or 4a HCV proteases was comparable (within 10-fold) to that against
HCV proteases of genotype 1a or 1b. Computational modeling analysis suggests
that genotype-specific signature residues, such as residues 78-80 of
genotype 2 or residue 168 of genotype 3, may not significantly affect the
binding of telaprevir to these HCV proteases. In addition, polymorphic
variations within each genotype or subtype did not seem to have dramatic
impact on the inhibition by telaprevir, which is consistent with the
observation that most of the polymorphic variations are located far away
>from the active site of the HCV protease.
Conclusions: These in vitro studies demonstrate that telaprevir is a potent
inhibitor of HCV NS3•4A proteases from genotypes 2, 3, or 4. These results
support the clinical investigation of the antiviral activity of telaprevir
in patients infected with genotypes 2, 3 or 4 HCV.