Required concentration index quantifies effective drug combinations against hepatitis C virus infection.

Successful clinical drug development requires rational design of combination treatments based on preclinical data. Anti-hepatitis C virus (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-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 1b and 2a. 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.

Citation

Yusuke Kakizoe, Yoshiki Koizumi, Yukino Ikoma, Hirofumi Ohashi, Takaji Wakita, Shingo Iwami, Koichi Watashi. Required concentration index quantifies effective drug combinations against hepatitis C virus infection. Theoretical biology & medical modelling. 2021 Jan 09;18(1):4

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PMID: 33422060

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