TY - JOUR
T1 - Required concentration index quantifies effective drug combinations against hepatitis C virus infection
AU - Kakizoe, Yusuke
AU - Koizumi, Yoshiki
AU - Ikoma, Yukino
AU - Ohashi, Hirofumi
AU - Wakita, Takaji
AU - Iwami, Shingo
AU - Watashi, Koichi
N1 - Funding Information:
This study was supported in part by Grants-in-Aid for JSPS Scientific Research (KAKENHI) Scientific Research B 18KT0018 (to S.I.), 18H01139 (to S.I.), 16H04845 (to S.I.), 17H04085 (to K.W.), Scientific Research in Innovative Areas 19H04839 (to S.I.), 18H05103 (to S.I.); AMED CREST 19 g1310002 (to S.I.); AMED J-PRIDE 19fm0208006s0103 (to S.I.), 19fm0208014h0003 (to S.I.), 19fm0208019h0103 (to S.I.), 19fm0208019j0003 (to K.W.); AMED Research Program on HIV/AIDS 19fk0410023s0101 (to S.I.); Research Program on Emerging and Re-emerging Infectious Diseases 19fk0108050h0003 (to S.I.); Program for Basic and Clinical Research on Hepatitis 19fk0210036h0502 (to S.I.), 19fk0210036j0002 (to K.W.); Program on the Innovative Development and the Application of New Drugs for Hepatitis B 19fk0310114h0103 (to S.I.), 19fk0310114j0003 (to K.W.), 19fk0310101j1003 (to K.W.), 19fk0310103j0203 (to K.W.); JST MIRAI (to S.I. and K.W.); JST CREST (to S.I. and K.W.); Mitsui Life Social Welfare Foundation (to S.I. and K.W.); Shin-Nihon of Advanced Medical Research (to S.I.); Suzuken Memorial Foundation (to S.I.); Life Science Foundation of Japan (to S.I.); SECOM Science and Technology Foundation (to S.I.); The Japan Prize Foundation (to S.I.); Toyota Physical and Chemical Research Institute (to S.I.); Fukuoka Financial Group, Inc. (to S.I.); Kyusyu Industrial Advancement Center Gapfund Program (to S.I.); Foundation for the Fusion Of Science and Technology (to S.I.); The Yasuda Medical Foundation (to K.W.); Smoking Research Foundation (to K.W.); Takeda Science Foundation (to K.W.); Mochida Memorial Foundation for Medical and Pharmaceutical Research (to K.W.).
Funding Information:
We are grateful to Dr. Kunitada Shimotohno at National Center for Global Health and Medicine for providing LucNeo#2 cells. SCY635 was kindly provided by Scynexis, Inc. We appreciate the editorial assistance provided by Dr. Senko Tsukuda at Department of Virology II, National Institute of Infectious.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85099000130&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85099000130&partnerID=8YFLogxK
U2 - 10.1186/s12976-020-00135-6
DO - 10.1186/s12976-020-00135-6
M3 - Article
C2 - 33422060
AN - SCOPUS:85099000130
SN - 1742-4682
VL - 18
JO - Theoretical Biology and Medical Modelling
JF - Theoretical Biology and Medical Modelling
IS - 1
M1 - 4
ER -
