gave better results. A combination of simeprevir or NS5A replication complex inhibitor,
daclatasvir or ledipasvir with Sofosbuvir with or without RBV for a 12 weeks treatment course
in HCV genotype1 saw a sustained virological response (SVR) of more than 90% (Lin).
Additionally, regimens based on ritonavir-boosted NS3/4A protease inhibitor, ABT-450/r
combined with or without RBV for 12 weeks treatment course in HCV genotype 1 have also
produced similar results (Rosenquist).
Development of NS3/4A Protease Inhibitors (PIs), telaprevir faced a lot of hurdles as it
had to be put on hold due to its performance in a standard IC
assay. It took data from new
experiments and hypothesis to justify further investment in the development of telaprevir. The
drug was approved in Europe in 2011 for the treatment of HCV genotype 1. Nucleotide NS5B
inhibitor, Sofosbuvir, also known, as GS-7977 discovery revolutionized the management of
Hepatitis C Virus infection. It was used in the initial evaluation with RBV and PEG-IFN. The
valuable features of Sofosbuvir which include its excellent tolerability, pan genotypic activity,
and safety profile makes it a powerful weapon in the treatment of HCV infection (Zappulo). The
highly selective NS5A inhibitor, Daclatasvir (BMS790052) was developed by Bristol-Myers
Squibb. It has a broad coverage of HCV genotypes in vitro. Daclatasvir (BMS790052 was
approved in July 2015 for use in treatment of HCV genotype 1 and 3
Therapy for HCV infection was at the pace of snail as it remained nearly the same
between 2001 and 2011. The development of specific compounds against HCV took a very long
time. The hurdles that slowed the process include the limitation of animal models for
experimentation and in vitro systems. Also, there was a low rate of discovery of suitable
candidate molecules and the balance between resistance to the selected antiviral drugs, toxicity,
and efficacy. The development of an in vitro virus propagation system by Weller, Robbins, and
Enders in 1951 was a huge breakthrough in this field. This helped in the study of viruses. The
inception of 9-(2-hydroxy ethoxy methyl) guanine (Acyclovir) improved the understanding of
virus-host interaction. It was the first highly effective antiviral drug.
DAAs approval has substantially improved therapeutic options for treatment of HCV
infection. An era of development of new DAAs for HCV treatment is currently emerging.
Several other Direct-acting antivirals are being developed such as Protease inhibitors:
asunaprevir, faldaprevir, vaniprevir, danoprevir, GS-9451, MK5172, ABT-450-ritonavir; NS5A
inhibitors:daclatasvir, MK-8742, PPI-668, GS-5816, ombitasvir and ledipasvir; NS5b