Many studies have been performed to develop an antiviral therapy against the hepatitis C virus (HCV)
infections. The usual treatment for HCV infection is a combination of PEGylated interferon and ribavirin which
offer restricted efficiency and major side effects. Thus, recent development in molecular biology of HCV and its
life cycle led to the design of many drugs that target viral proteins and host factors required for viral replication.
These drugs were named as direct-acting antivirals (DAAs) that were specifically designed for inhibition of viral
life cycle, promising tolerability, short duration of treatment, higher barrier to resistance, and fewer drug interactions.
The use of DAAs for the treatment of HCV infection resulted in high virological cure rates in patients.
However, the use of combined DAA regimens may present drug interactions especially in patients under treatment
for other co-morbidities. On the other hand, drug resistance against virus infection determines the success of
long-term therapy. High genetic diversity among HCV virions due to error-prone polymerase activity led to the
reduced susceptibility to DAA-therapy. Therefore, preclinical and clinical analysis of HCV resistance to novel
drugs is needed. In this review, we describe pharmaceutical approaches for HCV treatment, structural and functional
properties of DAAs, the principles of HCV drug-drug interaction, and finally HCV resistance to DAAs.