NS5b GT2

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Sofosbuvir

 EC50 (uM)Fold-shiftPhenotypeReplicative Fitness (5)Clinical RASReferenceComments                         
WT0.0371xlikely susceptible1002
H25R0.9xlikely susceptible908
K51R0.9xlikely susceptible945
S62A [Conflicting WT, not used in algorithm]resistance possibleYes7Clincal TE RAS (7)
K100Q1xlikely susceptible1065
L159F4EASL 2016 guidelines
T179A1.1xlikely susceptible2
A252Vresistance possibleYes7Clincal TE RAS (7)
S282T (GT2a)0.1752.8xresistance likely112,1,3,4,5, 6TE RAV (3, 6)
S282T (GT2b)16.2xresistance likely115
S282Rresistance likelycatalytic triad
S282Gresistance likelycatalytic triad
T286P1.3xlikely susceptible1225
M289Iresistance possibleYes6Clincial TE RAV, 1% (6)
M289L2.0xlikely susceptible642,5
I293L1.3xlikely susceptible2
M434T0.9xlikely susceptible2
H479P1.0xlikely susceptible2
T483M0.9xlikely susceptible855
R498K1.3xlikely susceptible1265GT2b
S549N0.8xlikely susceptible745
T179A+M289L2.1xlikely susceptible2
S282T+M289L 6.3xresistance likely222,5replicon selected
S282T+R498K14xresistance likely145GT2b
M289L+I293L2.5xresistance possible2replicon selected
T179A+M289L+I293L3.5xresistance likely2
T179A+S282T+I293L8.3xresistance likely2replicon selected
T179A+S282T+M289L+I293L9.5xresistance likely2replicon selected
S282T+M289L+H479P7.4xresistance likely2replicon selected
S282T+M289L+I293L5.6xresistance likely2replicon selected
S282T+M289L+I293L+H479P8.4xresistance likely2replicon selected
S282T+M289L+I293L+M434T7.1xresistance likely2replicon selected
T179A+S282T+I293L+H479P9xresistance likely2replicon selected
T179A+S282T+M289L+H479P11.4xresistance likely2replicon selected
T179A+S282T+M289L+I293L+H479P11.8xresistance likely2replicon selected
T179A+S282T+M289L+I293L+M434T10.6xresistance likely2replicon selected
1. Harvoni US Product Lable
2. Lam et al (2012) AAC 56:3359-3368
3. Lontok et al. (2015) Hepatology 62.5: 1623-1632.
4. EASL Guidelines 2016
5. Xu et al. (2017) Antiviral therapy 22:587-97.
6. FDA Vosevi Microbiology Reviews 209195Orig1s000MicroR
7. FDA Microbiology/Virology Reviews Epclusa_ 208341Orig1s000 (2015)
8. Svarovskaia ES, et al. 2014. Clinical Infectious Diseases 59: 1666-74