efficacy rate of interferon plus ribavirin varied within 44–46% while it increases up to 90% by direct-acting antivirals such as NS5B inhibitors/ Data on the frequency of side effects may vary between researches for both drug categories. Nevertheless, there is a significant difference between the safety profiles of NS5B inhibitors, particularly sofosbuvir and the combination of interferon and ribavirin. Comparing interferon containing therapies, sofosbuvir does not cause neutropenia, thrombocytopenia, or any other serious adverse effects. Common side effects associated with sofosbuvir are headache, tiredness, insomnia, dizziness, itching, infections of upper respiratory tract, rashes, back pain, anemia, and lymphopenia. With the advent of direct-acting antivirals, the duration of the hepatitis treatment has also been impressively reduced. Severity of adverse effects is strongly associated with duration of therapy and the dose used for hepatitis C treatment. Therefore, direct-acting antivirals have become the initial treatment used for most patients with chronic hepatitis C. Hepatitis C virus Hepatitis C virus belongs to the family Flaviviridae and genus hepavirus. It is a small enveloped, single stranded RNA virus with positive polarity. A lipid bilayer which contains two viral glycoproteins, E1 and E2, forms the envelope and virion. Hepatitis C virus is transmitted through exposure to infected blood or body fluids, and the most common route is through injection by infected needles. In the beginning of the hepatitis C virus life cycle, virions bind to specific receptors on hepatocytes. The virus is internalized and the nucleocapsid is released into the cytoplasm of the hepatocyte after binding with the receptor. The NS5B protein, which is an RNA-dependent RNA polymerase, catalyzes hepatitis C virus replication. The hepatitis C virus can cause acute infection but most patients are asymptomatic upon exposure. About one-third of patients develop symptoms such as fatigue, arthralgia and jaundice. About 15–45% of patients diagnosed with acute infection may clear the virus without treatment. After acute infection, most infected patients will develop chronic infection which increases the risk for later developing life-threatening conditions, like liver cirrhosis and hepatocellular carcinoma. In 2015, about 71 million individuals throughout the world were living with chronic hepatitis C and there were 1.75 million new hepatitis C virus infections that same year. With highly effective direct-acting antivirals, hepatitis C can be cured within 2 to 3 months. NS5B receptor NS5B is a viral protein that can be found in the hepatitis C virus and is an important enzyme in the replication