The HCV genome. NS5A in the bottom row, second from the right.
Nonstructural protein 5A (NS5A) inhibitors are direct acting antiviral agents (DAAs) that target viral proteins , and their development was a culmination of increased understanding of the viral life cycle combined with advances in drug discovery technology.[ 1] [ 2] However, their mechanism of action is complex and not fully understood.[ 2] NS5A inhibitors were the focus of much attention when they emerged as a part of the first curative treatment for hepatitis C virus (HCV) infections in 2014.[ 3] Favorable characteristics have been introduced through varied structural changes, and structural similarities between NS5A inhibitors that are clinically approved are readily apparent.[ 4] [ 5] Despite the recent introduction of numerous new antiviral drugs, resistance is still a concern and these inhibitors are therefore always used in combination with other drugs.[ 6] [ 7]
^ Gogela, Neliswa A.; Lin, Ming V.; Wisocky, Jessica L.; Chung, Raymond T. (12 March 2015). "Enhancing Our Understanding of Current Therapies for Hepatitis C Virus (HCV)" . Current HIV/AIDS Reports . 12 (1): 68–78. doi :10.1007/s11904-014-0243-7 . PMC 4373591 . PMID 25761432 .
^ a b Pawlotsky, Jean-Michel (August 2013). "NS5A inhibitors in the treatment of hepatitis C" . Journal of Hepatology . 59 (2): 375–382. doi :10.1016/j.jhep.2013.03.030 . PMID 23567084 .
^ Do, Albert; Mittal, Yash; Liapakis, AnnMarie; Cohen, Elizabeth; Chau, Hong; Bertuccio, Claudia; Sapir, Dana; Wright, Jessica; Eggers, Carol; Drozd, Kristine; Ciarleglio, Maria; Deng, Yanhong; Lim, Joseph K.; Jhaveri, Ravi (27 August 2015). "Drug Authorization for Sofosbuvir/Ledipasvir (Harvoni) for Chronic HCV Infection in a Real-World Cohort: A New Barrier in the HCV Care Cascade" . PLOS ONE . 10 (8): e0135645. Bibcode :2015PLoSO..1035645D . doi :10.1371/journal.pone.0135645 . PMC 4552165 . PMID 26312999 .
^ Tong, Ling; Yu, Wensheng; Coburn, Craig A.; Meinke, Peter T.; Nair, Anilkumar G.; Dwyer, Michael P.; Chen, Lei; Selyutin, Oleg; Rosenblum, Stuart B.; Jiang, Yueheng; Fells, James; Hu, Bin; Zhong, Bin; Soll, Richard M.; Liu, Rong; Agrawal, Sony; Xia, Ellen; Zhai, Ying; Kong, Rong; Ingravallo, Paul; Nomeir, Amin; Asante-Appiah, Ernest; Kozlowski, Joseph A. (July 2016). "Alternative core development around the tetracyclic indole class of HCV NS5A inhibitors" . Bioorganic & Medicinal Chemistry Letters . 26 (20): 5132–5137. doi :10.1016/j.bmcl.2016.07.057 . PMID 27634194 .
^ Lemm, J. A.; Leet, J. E.; O'Boyle, D. R.; Romine, J. L.; Huang, X. S.; Schroeder, D. R.; Alberts, J.; Cantone, J. L.; Sun, J.-H.; Nower, P. T.; Martin, S. W.; Serrano-Wu, M. H.; Meanwell, N. A.; Snyder, L. B.; Gao, M. (16 May 2011). "Discovery of Potent Hepatitis C Virus NS5A Inhibitors with Dimeric Structures" . Antimicrobial Agents and Chemotherapy . 55 (8): 3795–3802. doi :10.1128/AAC.00146-11 . PMC 3147613 . PMID 21576451 .
^ Fridell, R. A.; Qiu, D.; Wang, C.; Valera, L.; Gao, M. (28 June 2010). "Resistance Analysis of the Hepatitis C Virus NS5A Inhibitor BMS-790052 in an In Vitro Replicon System" . Antimicrobial Agents and Chemotherapy . 54 (9): 3641–3650. doi :10.1128/AAC.00556-10 . PMC 2935007 . PMID 20585111 .
^ Asselah, Tarik; Boyer, Nathalie; Saadoun, David; Martinot-Peignoux, Michele; Marcellin, Patrick (January 2016). "Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives" . Liver International . 36 : 47–57. doi :10.1111/liv.13027 . PMID 26725897 .