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Comment
. 2017 Jun 6;114(23):E4527-E4529.
doi: 10.1073/pnas.1705234114. Epub 2017 May 16.

Reply to Padmanabhan and Dixit: Hepatitis C virus entry inhibitors for optimally boosting direct-acting antiviral-based treatments

Hirofumi Ohashi  1   2 , Yoshiki Koizumi  3 , Kento Fukano  1   4 , Takaji Wakita  1 , Alan S Perelson  5 , Shingo Iwami  6   7   8 , Koichi Watashi  9   2   8
Affiliations
Comment

Reply to Padmanabhan and Dixit: Hepatitis C virus entry inhibitors for optimally boosting direct-acting antiviral-based treatments

Hirofumi Ohashi et al. Proc Natl Acad Sci U S A. .
No abstract available

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Conflict of interest statement

Conflict of interest statement: The authors declare that they have no competing interests, except A.S.P., who has consulted for Gilead Sciences, Merck, Bristol Myers Squibb, Achillion, and Santaris Pharma.

Figures

Fig. 1.
Fig. 1.
Evaluation of anti-HCV drug combination with DAAs and entry inhibitors. (A) Schematic model of the targets of entry inhibitors and DAAs used in this study. NI, nucleoside-type polymerase inhibitor; NNI, nonnucleoside-type polymerase inhibitor; PI, protease inhibitor. (B) Schematic representation of the assay to evaluate the anti-HCV activity of the drugs. Upon drug treatment, Huh7.5.1 cells were inoculated with HCV JFH-1 at a multiplicity of infection of 0.5 for 4 h, and were cultured for an additional 48 h. Anti-HCV E2 antibodies were used by preincubation with HCV for 1 h and coincubation with HCV for 4 h. The infection level of HCV was quantified by measuring intracellular HCV RNA. (C) IIP values for DAAs in our study (2) and the HCV entry inhibitors (AR3A, BLT-1, and erlotinib) at a drug concentration D=100×IC50 (IIP100) determined by extrapolation. (D) Bliss-estimated IIP100Bcom of triple-drug combination, including DAAs and the entry inhibitors. ASV, asunaprevir; DAS, dasabuvir; DCV, daclatasvir; LDV, ledipasvir; SOF, sofosbuvir; SMV, simeprevir.
See this image and copyright information in PMC

Comment on

References

    1. Padmanabhan P, Dixit NM. Inhibitors of hepatitis C virus entry may be potent ingredients of optimal drug combinations. Proc Natl Acad Sci USA. 2017;114:E4524–E4526. - PMC - PubMed
    1. Koizumi Y, et al. Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection. Proc Natl Acad Sci USA. 2017;114:1922–1927. - PMC - PubMed
    1. Shen L, et al. Dose-response curve slope sets class-specific limits on inhibitory potential of anti-HIV drugs. Nat Med. 2008;14:762–766. - PMC - PubMed
    1. Law M, et al. Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge. Nat Med. 2008;14:25–27. - PubMed
    1. Nieland TJ, Penman M, Dori L, Krieger M, Kirchhausen T. Discovery of chemical inhibitors of the selective transfer of lipids mediated by the HDL receptor SR-BI. Proc Natl Acad Sci USA. 2002;99:15422–15427. - PMC - PubMed

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