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bioRxiv · 10.1101/2020.01.09.899807

Required concentration index quantifies effective drug combinations against HCV infection

Iwami, S.·Kakizoe, Y.·Koizumi, Y.·Ikoma, Y.·Ohashi, H.·Wakita, T.·Watashi, K.
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Abstract

Successful clinical drug development requires rational design of combination treatments based on preclinical data. Anti-HCV drugs exhibit significant diversity in antiviral effect. Dose-response assessments can be used to determine parameters profiling the diverse antiviral effect during combination treatment. In the current study, a combined experimental and mathematical approaches were used to compare and score different combinations of anti-hepatitis C virus (HCV) treatments. A "required concentration index" was generated and used to rank the antiviral profile of possible double- and triple-drug combinations against HCV genotype 1 and 2. Rankings varied based on target HCV genotype. Interestingly, multidrug (double and triple) treatment not only augmented antiviral activity, but also reduced genotype-specific efficacy, suggesting another advantage of multidrug treatment. The current study provides a quantitative method for profiling drug combinations against viral genotypes, to better inform clinical drug development.

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Iwami, S., Kakizoe, Y., Koizumi, Y., Ikoma, Y., Ohashi, H., Wakita, T., Watashi, K.. 2020-01-09. Required concentration index quantifies effective drug combinations against HCV infection. https://doi.org/10.1101/2020.01.09.899807

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