Open AccessProfiling the physiological pitfalls of anti‐hepatitis C direct‐acting agents in budding yeast
Author(s) -
Yahya Galal,
Hashem Mohamed Nashwa,
Pijuan Jordi,
Seleem Noura M.,
Mosbah Rasha,
Hess Steffen,
Abdelmoaty Ahmed A.,
Almeer Rafa,
AbdelDaim Mohamed M.,
Shulaywih Alshaman Hamoud,
Juraiby Ibrahim,
Metwally Kamel,
Storchova Zuzana
Publication year - 2021
Publication title -
microbial biotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.287
H-Index - 74
ISSN - 1751-7915
DOI - 10.1111/1751-7915.13904
Subject(s) - daclatasvir , sofosbuvir , endoplasmic reticulum , virology , hepatitis c virus , hepatocellular carcinoma , adverse effect , medicine , pharmacology , biology , virus , cancer research , biochemistry , ribavirin
Summary Sofosbuvir and Daclatasvir are among the direct‐acting antiviral (DAA) medications prescribed for the treatment of chronic hepatitis C (CHC) virus infection as combination therapy with other antiviral medications. DAA‐based therapy achieves high cure rates, reaching up to 97% depending on the genotype of the causative hepatitis C virus (HCV). While DAAs have been approved as an efficient and well‐tolerated therapy for CHC, emerging concerns about adverse cardiac side effects, higher risk of recurrence and occurrence of hepatocellular carcinoma (HCC) and doubts of genotoxicity have been reported. In our study, we investigated in detail physiological off‐targets of DAAs and dissected the effects of these drugs on cellular organelles using budding yeast, a unicellular eukaryotic organism. DAAs were found to disturb the architecture of the endoplasmic reticulum (ER) and the mitochondria, while showing no apparent genotoxicity or DNA damaging effect. Our study provides evidence that DAAs are not associated with genotoxicity and highlights the necessity for adjunctive antioxidant therapy to mitigate the adverse effects of DAAs on ER and mitochondria.