Generic placeholder image

The Natural Products Journal

Editor-in-Chief

ISSN (Print): 2210-3155
ISSN (Online): 2210-3163

Systematic Review Article

A Systematic Review on the Evolution of Natural Mutation-dependent Antiviral Drug Resistance in Hepatitis C Virus (HCV) Genotypes Prevalent in Saudi Arabia: A Genomic and Therapeutic Perspective

In Press, (this is not the final "Version of Record"). Available online 03 April, 2024
Author(s): Mohammad Asrar Izhari*
Published on: 03 April, 2024

Article ID: e030424228571

DOI: 10.2174/0122103155291056240327033157

Price: $95

Abstract

Background: The characterization of resistance-associated amino acid substitution (RAAS) in direct-acting antivirals (DAA) molecular targets could reshape the treatment strategy for HCV infection. Hence, this review aimed to provide evidence on the impact of the RAASs on DAA treatment for HCV.

Methods: PRISMA model was followed for the literature survey and evaluation (sources: PubMed, Sci-Hub, and Google Scholar). RAASs in DAA target proteins and their locations were mapped on 3-D proteins using two reference protein sequences: NS3/ID: AAA72945.1 and NS5A/NS5B/ID: NP_671491.1. NCBI-Basic Local Alignment Tool, UniProt and AlphaFold2/MMSeqs2, PyMol, and R-base/R-studio were used for alignment, retrieval of protein sequences, 3-D protein structure modeling, visualization of locations of RAASs, and diagrammatic representations, respectively.

Results: Genotype 4 afterwards genotype 1 was the most prevalent in Saudi Arabia. L2003M, Y2065N, M2000T, L2003V, and Q2002H RAASs were anti-NS5A inhibitor. NS5A-Q2002H was anti-daclatasvir in genotype 4. NS5A-Y2065H and NS5B-S2702T in genotype 1 were antisofosbuvir- resistant. NS3-A1182V, NS3-Q1106K/R, and NS3-T1080S RAASs exhibited resistance to double antivirals. NS3-D1194A RAAS was a multi-drug resistant variant (against 3 DAAs). NS3- V1062A, NS3-D1194G, NS3-D1194E/T, NS3- S1148R, NS3-V1196A, NS3-V1062LNS3-S1148A, and NS3-S1148G RAASs in genotype 1 were single drug-resistant variants. NS3- S1148R and NS3- S1148A in genotypes 2 and 5 were anti-simeprevir-resistant variants.

Conclusions: An array of identified RAASs, RAAS-dependent DAA treatment failure, and recommended combination DAA therapy in such clinical scenarios of RAASs are the significant outcomes of this research. RAAS-linked in vitro and in vivo resistance profiling at genotype/sub-genotype level will be crucial in treatment choice and for future DAA design strategies.

[1]
Saravanan, S.; Velu, V.; Kumarasamy, N.; Nandakumar, S.; Murugavel, K.G.; Balakrishnan, P.; Suniti, S.; Thyagarajan, S.P. Coinfection of hepatitis B and hepatitis C virus in HIV-infected patients in south India. World J. Gastroenterol., 2007, 13(37), 5015-5020.
[http://dx.doi.org/10.3748/wjg.v13.i37.5015] [PMID: 17854146]
[2]
Mauger, D.M.; Golden, M.; Yamane, D.; Williford, S.; Lemon, S.M.; Martin, D.P.; Weeks, K.M. Functionally conserved architecture of hepatitis C virus RNA genomes. Proc. Natl. Acad. Sci., 2015, 112(12), 3692-3697.
[http://dx.doi.org/10.1073/pnas.1416266112] [PMID: 25775547]
[3]
Wedemeyer, H.; Dore, G.J.; Ward, J.W. Estimates on HCV disease burden worldwide – filling the gaps. J. Viral Hepat., 2015, 22(S1), 1-5.
[http://dx.doi.org/10.1111/jvh.12371] [PMID: 25560838]
[4]
Alter, H.J.; Seeff, L.B. Recovery, persistence, and sequelae in hepatitis C virus infection: A perspective on long-term outcome. Semin. Liver Dis., 2000, 20(1), 17-35.
[http://dx.doi.org/10.1055/s-2000-9505]
[5]
Younossi, Z.M.; Tanaka, A.; Eguchi, Y.; Lim, Y.S.; Yu, M.L.; Kawada, N.; Dan, Y.Y.; Rooney, B.C.; Negro, F.; Mondelli, M.U. The impact of hepatitis C virus outside the liver: Evidence from Asia. Liver Int., 2017, 37(2), 159-172.
[http://dx.doi.org/10.1111/liv.13272] [PMID: 27748564]
[6]
Williams, R. Global challenges in liver disease. Hepatology, 2006, 44(3), 521-526.
[http://dx.doi.org/10.1002/hep.21347] [PMID: 16941687]
[7]
Manns, M.P.; Buti, M.; Gane, E.; Pawlotsky, J.M.; Razavi, H.; Terrault, N.; Younossi, Z. Hepatitis C virus infection. Nat. Rev. Dis. Primers, 2017, 3(1), 17006.
[http://dx.doi.org/10.1038/nrdp.2017.6] [PMID: 28252637]
[8]
Cougot, D.; Neuveut, C.; Buendia, M.A. HBV induced carcinogenesis. J. Clin. Virol., 2005, 34(S1), S75-S78.
[http://dx.doi.org/10.1016/S1386-6532(05)80014-9] [PMID: 16461228]
[9]
Kuna, L.; Jakab, J.; Smolic, R.; Wu, G.Y.; Smolic, M. HCV extrahepatic manifestations. J. Clin. Transl. Hepatol., 2019, 7(2), 172-182.
[PMID: 31293918]
[10]
Aljumah, A.A.; Abaalkhail, F.; Al-Ashgar, H.; Assiri, A.; Babatin, M.; Al Faleh, F.; Alghamdi, A.; Hakeem, A.R.; Hashim, A.; Alqutub, A. Epidemiology, disease burden, and treatment strategies of chronic hepatitis C virus infections in Saudi Arabia in the new treatment paradigm shift. Saudi J. Gastroenterol., 2016, 22(4), 269.
[11]
Farci, P. New insights into the HCV quasispecies and compartmentalization. Semin. Liver Dis., 2011, 31(4), 356-374.
[http://dx.doi.org/10.1055/s-0031-1297925]
[12]
Andino, R.; Domingo, E. Viral quasispecies. Virology, 2015, 479-480, 46-51.
[http://dx.doi.org/10.1016/j.virol.2015.03.022] [PMID: 25824477]
[13]
Keikha, M.; Eslami, M.; Yousefi, B.; Hassanzadeh, A.M.; Kamali, A.; Yousefi, M.; Karbalaei, M. HCV genotypes and their determinative role in hepatitis C treatment. Virusdisease, 2020, 31(3), 235-240.
[http://dx.doi.org/10.1007/s13337-020-00592-0] [PMID: 32904762]
[14]
Jamall, I.S.; Yusuf, S.; Azhar, M.; Jamall, S. Is pegylated interferon superior to interferon, with ribavarin, in chronic hepatitis C genotypes 2/3? World J. Gastroenterol., 2008, 14(43), 6627-6631.
[http://dx.doi.org/10.3748/wjg.14.6627] [PMID: 19034963]
[15]
Dua, A.; Desai, S.S.; Kumar, N.; Heller, J. Epidemiology and treatment strategies of iliac vein thrombophlebitis. Vascular, 2015, 23(6), 599-601.
[http://dx.doi.org/10.1177/1708538114565693] [PMID: 25575974]
[16]
Zein, N.N. Clinical significance of hepatitis C virus genotypes. Clin. Microbiol. Rev., 2000, 13(2), 223-235.
[http://dx.doi.org/10.1128/CMR.13.2.223] [PMID: 10755999]
[17]
Cai, L.N.; Zhu, S.W.; Zhou, C.; Wang, Y.B.; Jiang, N.Z.; Chen, H.; Tang, X.Y.; Wang, J.H.; Chen, X.; Hu, W.J.; Chen, B.W.; Chen, B.A. Infection status of HBV, HCV and HIV in voluntary blood donors of Chinese Nanjing area during 2010-2013. J. Exp. Hematol., 2014, 22(4), 1089-1093.
[http://dx.doi.org/10.7534/j.issn.1009-2137.2014.04.038] [PMID: 25130834]
[18]
Wiley, T.E.; Brown, J.; Chan, J. Hepatitis C infection in African Americans: its natural history and histological progression. Am. J. Gastroenterol., 2002, 97(3), 700-706.
[http://dx.doi.org/10.1111/j.1572-0241.2002.05555.x] [PMID: 11922566]
[19]
Bawazir, A.; AlGusheri, F.; Jradi, H.; AlBalwi, M.; Abdel-Gader, A.G. Hepatitis C virus genotypes in Saudi Arabia: A future prediction and laboratory profile. Virol. J., 2017, 14(1), 208.
[http://dx.doi.org/10.1186/s12985-017-0873-7] [PMID: 29096662]
[20]
Aziz, H.; Raza, A.; Murtaza, S.; Waheed, Y.; Khalid, A.; Irfan, J.; Samra, Z.; Athar, M.A. Molecular epidemiology of hepatitis C virus genotypes in different geographical regions of Punjab Province in Pakistan and a phylogenetic analysis. Int. J. Infect. Dis., 2013, 17(4), e247-e253.
[http://dx.doi.org/10.1016/j.ijid.2012.09.017] [PMID: 23183233]
[21]
Zein, N.N.; Persing, D.H. Hepatitis C genotypes: Current trends and future implications. Mayo Clin. Proc., 1996, 71(5), 458-462.
[http://dx.doi.org/10.4065/71.5.458] [PMID: 8628025]
[22]
Abozaid, S.M.; Shoukri, M.; Qahtani, A.A.; Ahdal, A.M.N. Prevailing genotypes of hepatitis C virus in Saudi Arabia: A systematic analysis of evidence. Ann. Saudi Med., 2013, 33(1), 1-5.
[http://dx.doi.org/10.5144/0256-4947.2013.1] [PMID: 23458931]
[23]
Almosa, F.A.M.; Alnasser, A.H.A.; Al-Tawfiq, J.A. Distribution of hepatitis C virus (HCV) genotypes in a Saudi Arabian hospital during the 2015-2020 period. Infez. Med., 2021, 29(3), 450-455.
[http://dx.doi.org/10.53854/liim-2903-16] [PMID: 35146350]
[24]
Ward, S.; Lauer, G.; Isba, R.; Walker, B.; Klenerman, P. Cellular immune responses against hepatitis C virus: The evidence base 2002. Clin. Exp. Immunol., 2002, 128(2), 195-203.
[http://dx.doi.org/10.1046/j.1365-2249.2002.01840.x] [PMID: 11985510]
[25]
Lu, J.; Feng, Y.; Chen, L.; Zeng, Z.; Liu, X.; Cai, W.; Wang, H.; Guo, X.; Zhou, H.; Tao, W.; Xie, Q. Subtype-specific prevalence of hepatitis C virus NS5A resistance associated substitutions in Mainland China. Front. Microbiol., 2019, 10, 535.
[http://dx.doi.org/10.3389/fmicb.2019.00535] [PMID: 30941111]
[26]
Dietz, J.; Müllhaupt, B.; Buggisch, P.; Graf, C.; Peiffer, K.H.; Matschenz, K.; Schattenberg, J.M.; Antoni, C.; Mauss, S.; Niederau, C.; Discher, T.; Trauth, J.; Dultz, G.; zur Wiesch, S.J.; Piecha, F.; Klinker, H.; Müller, T.; Berg, T.; Haefelin, N.C.; Berg, C.P.; Zeuzem, S.; Sarrazin, C.; Balavoine, J.; Giostra, E.; Berning, M.; Hampe, J.; Canbay, A.; Steckstor, W.; Schmiegel, W.; Brockmeyer, N.H.; De Gottardi, A.; Rauch, A.; Semmo, N.; Fischer, J.; Gress, M.; Heinzow, H.; Hilgard, G.; Schmidt, H.; Herrmann, A.; Stallmach, A.; Hoffmann, D.; Protzer, U.; Klinker, H.; Schulze, P.; Kodal, A.; Kremer, A.; Siebler, J.; Löbermann, M.; Götze, T.; Weigt, J.; Lohse, A.; Von Felden, J.; Jordan, S.; Lange, C.M.; Zachoval, R.; Mayerle, J.; Maieron, A.; Moradpour, D.; Chave, J-P.; Moreno, C.; Muche, M.; Epple, H-J.; Müller-Schilling, M.; Kocheise, F.; Müllhaupt, B.; Port, K.; Deterding, K.; Wedemeyer, H.; Cornberg, M.; Manns, M.; Reinhardt, L.; Ellenrieder, V.; Rissland, J.; Semela, D.; Spengler, U.; Rockstroh, J.; Roeb, E.; Sprinzl, M.; Galle, P.; Stauber, R.; Stremmel, W.; Strey, B.; Thimme, R.; Boettler, T.; Tacke, F.; Teufel, A.; Vogelmann, R.; Ebert, M.; Tomasiewicz, K.; Trautwein, C.; Koenen, T.; Weber, T.; Wietzke-Braun, P.; Günther, R.; Zizer, E.; Backhus, J.; Seufferlein, T.; Angeli, W.; Beckebaum, S.; Doberauer, C.; Durmashkina, E.; Hackelsberger, A.; Erhardt, A.; Garrido-Lüneburg, A.; Gattringer, H.; Genné, D.; Gschwantler, M.; Gundling, F.; Hametner, S.; Schöfl, R.; Hartmann, C.; Heyer, T.; Hirschi, C.; Jussios, A.; Kanzler, S.; Kordecki, N.; Kraus, M.; Kullig, U.; Wollschläger, S.; Magenta, L.; Terziroli Beretta-Piccoli, B.; Menges, M.; Mohr, L.; Muehlenberg, K.; Niederau, C.; Paulweber, B.; Petrides, A.; Pinkernell, M.; Piso, R.; Rambach, W.; Reiser, M.; Riecken, B.; Rieke, A.; Roth, J.; Schelling, M.; Schlee, P.; Schneider, A.; Scholz, D.; Schott, E.; Schuchmann, M.; Schulten-Baumer, U.; Seelhoff, A.; Stich, A.; Stickel, F.; Ungemach, J.; Walter, E.; Weber, A.; Winzer, T.; Abels, W.; Adler, M.; Audebert, F.; Baermann, C.; Bästlein, E.; Barth, R.; Barthel, K.; Becker, W.; Behrends, J.; Benninger, J.; Berger, F.; Berzow, D.; Beyer, T.; Bierbaum, M.; Blaukat, O.; Bodtländer, A.; Böhm, G.; Börner, N.; Bohr, U.; Bokemeyer, B.; Bruch, H.R.; Bucholz, D.; Burkhard, O.; Busch, N.; Chirca, C.; Delker, R.; Diedrich, J.; Frank, M.; Diehl, M.; Dienethal, A.; Dietel, P.; Dikopoulos, N.; Dreck, M.; Dreher, F.; Drude, L.; Ende, K.; Ehrle, U.; Baumgartl, K.; Emke, F.; Glosemeyer, R.; Felten, G.; Hüppe, D.; Fischer, J.; Fischer, U.; Frederking, D.; Frick, B.; Friese, G.; Gantke, B.; Geyer, P.; Schwind, H.R.; Glas, M.; Glaunsinger, T.; Goebel, F.; Göbel, U.; Görlitz, B.; Graf, R.; Gruber, H.; Härter, G.; Herder, M.; Heuchel, T.; Heuer, S.; Höffl, K-H.; Hörster, H.; Sonne, J-U.; Hofmann, W.P.; Holst, F.; Hunstiger, M.; Hurst, A.; Guedes, J.E.; John, C.; Jung, M.; Kallinowski, B.; Kapzan, B.; Kerzel, W.; Khaykin, P.; Klarhof, M.; Klüppelberg, U. Wolfratshausen,; Klugewitz, K.; Knapp, B.; Knevels, U.; Kochsiek, T.; Körfer, A.; Köster, A.; Kuhn, M.; Langekamp, A.; Künzig, B.; Link, R.; Littman, M.; Löhr, H.; Lutz, T.; Knecht, G.; Lutz, U.; Mainz, D.; Mahle, I.; Maurer, P.; Mayer, C.; Meister, V.; Möller, H.; Heyne, R.; Moritzen, D.; Mroß, M.; Mundlos, M.; Naumann, U.; Nehls, O.; Ningel, K.R.; Oelmann, A.; Olejnik, H.; Gadow, K.; Pascher, E.; Petersen, J.; Philipp, A.; Pichler, M.; Polzien, F.; Raddant, R.; Riedel, M.; Rietzler, S.; Rössle, M.; Rufle, W.; Rump, A.; Schewe, C.; Hoffmann, C.; Schleehauf, D.; Schmidt, W.; Heinevetter, S.G.; von Fabris, S.J.; Schneider, L.; Schober, A.; Hahn, N.S.; Schwenzer, J.; Seegers, B.; Seidel, T.; Seitel, G.; Sick, C.; Simon, K.; Stähler, D.; Stenschke, F.; Steffens, H.; Stein, K.; Steinmüller, M.; Sternfeld, T.; Strey, B.; Svensson, K.; Tacke, W.; Teuber, G.; Teubner, K.; Thieringer, J.; Tomesch, A.; Trappe, U.; Ullrich, J.; Urban, G.; Usadel, S.; Von Lucadou, A.; Weinberger, F.; Werheid-Dobers, M.; Werner, P.; Winter, T.; Zehnter, E.; Zipf, A. Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure. J. Hepatol., 2023, 78(1), 57-66.
[http://dx.doi.org/10.1016/j.jhep.2022.08.016] [PMID: 36031158]
[27]
Sarrazin, C. Treatment failure with DAA therapy: Importance of resistance. J. Hepatol., 2021, 74(6), 1472-1482.
[http://dx.doi.org/10.1016/j.jhep.2021.03.004] [PMID: 33716089]
[28]
Li, D.K.; Chung, R.T. Overview of direct-acting antiviral drugs and drug resistance of hepatitis C virus. Methods Mol. Biol., 2019, 1911, 3-32.
[http://dx.doi.org/10.1007/978-1-4939-8976-8_1]
[29]
Malandris, K.; Kalopitas, G.; Theocharidou, E.; Germanidis, G. The role of RASs/RVs in the current management of HCV. Viruses, 2021, 13(10), 2096.
[http://dx.doi.org/10.3390/v13102096] [PMID: 34696525]
[30]
Harrington, P.R.; Komatsu, T.E.; Deming, D.J.; Donaldson, E.F.; O’Rear, J.J.; Naeger, L.K. Impact of hepatitis C virus polymorphisms on direct-acting antiviral treatment efficacy: Regulatory analyses and perspectives. Hepatology, 2018, 67(6), 2430-2448.
[http://dx.doi.org/10.1002/hep.29693] [PMID: 29194682]
[31]
Sarrazin, C. The importance of resistance to direct antiviral drugs in HCV infection in clinical practice. J. Hepatol., 2016, 64(2), 486-504.
[http://dx.doi.org/10.1016/j.jhep.2015.09.011] [PMID: 26409317]
[32]
Shahid, I.; Ibrahim, M.M.; Nawaz, M.U.; Imam, M.T.; AlMalki, W.H. Resistance-associated substitutions/variants correlate to therapeutic outcomes of novel direct-acting antivirals in different HCV genotype treated individuals. In: Genotyping; IntechOpen, 2018.
[http://dx.doi.org/10.5772/intechopen.76395]
[33]
Di Stefano, M.; Ismail, M.H.; Leitner, T.; Faleo, G.; Elmnan Adem, S.A.; Elamin, M.O.M.E.; Eltreifi, O.; Alwazzeh, M.J.; Fiore, J.R.; Santantonio, T.A. Genetic subtypes and natural resistance mutations in HCV genotype 4 infected Saudi Arabian patients. Viruses, 2021, 13(9), 1832.
[http://dx.doi.org/10.3390/v13091832] [PMID: 34578414]
[34]
Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann. Intern. Med., 2009, 151(4), 264-269. W64.
[http://dx.doi.org/10.7326/0003-4819-151-4-200908180-00135] [PMID: 19622511]
[35]
Liu, T.; Zheng, X.; Wang, J. Prediction of protein structural class for low-similarity sequences using support vector machine and PSI-BLAST profile. Biochimie, 2010, 92(10), 1330-1334.
[http://dx.doi.org/10.1016/j.biochi.2010.06.013] [PMID: 20600567]
[36]
Stover, N.A.; Cavalcanti, A.R. Using NCBI BLAST. In: Essential Laboratory Techniques; Wiley, 2017.
[http://dx.doi.org/10.1002/cpet.8]
[37]
Quek, J.P.; Ser, Z.; Chew, B.L.A.; Li, X.; Wang, L.; Sobota, R.M.; Luo, D.; Phoo, W.W. Dynamic interactions of post cleaved NS2B cofactor and NS3 protease identified by integrative structural approaches. Viruses, 2022, 14(7), 1440.
[http://dx.doi.org/10.3390/v14071440] [PMID: 35891424]
[38]
Jumper, J.; Evans, R.; Pritzel, A.; Green, T.; Figurnov, M.; Ronneberger, O.; Tunyasuvunakool, K.; Bates, R.; Žídek, A.; Potapenko, A.; Bridgland, A.; Meyer, C.; Kohl, S.A.A.; Ballard, A.J.; Cowie, A.; Paredes, R.B.; Nikolov, S.; Jain, R.; Adler, J.; Back, T.; Petersen, S.; Reiman, D.; Clancy, E.; Zielinski, M.; Steinegger, M.; Pacholska, M.; Berghammer, T.; Bodenstein, S.; Silver, D.; Vinyals, O.; Senior, A.W.; Kavukcuoglu, K.; Kohli, P.; Hassabis, D. Highly accurate protein structure prediction with AlphaFold. Nature, 2021, 596(7873), 583-589.
[http://dx.doi.org/10.1038/s41586-021-03819-2] [PMID: 34265844]
[39]
Wakita, T.; Pietschmann, T.; Kato, T.; Date, T.; Miyamoto, M.; Zhao, Z.; Murthy, K.; Habermann, A.; Kräusslich, H.G.; Mizokami, M.; Bartenschlager, R.; Liang, T.J. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat. Med., 2005, 11(7), 791-796.
[http://dx.doi.org/10.1038/nm1268] [PMID: 15951748]
[40]
Choo, Q.L.; Richman, K.H.; Han, J.H.; Berger, K.; Lee, C.; Dong, C.; Gallegos, C.; Coit, D.; Selby, M.R.; Barr, P.J. Genetic organization and diversity of the hepatitis C virus. Proc. Natl. Acad. Sci., 1991, 88(6), 2451-2455.
[http://dx.doi.org/10.1073/pnas.88.6.2451] [PMID: 1848704]
[41]
Choo, Q.L.; Kuo, G.; Weiner, A.J.; Overby, L.R.; Bradley, D.W.; Houghton, M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science, 1989, 244(4902), 359-362.
[http://dx.doi.org/10.1126/science.2523562] [PMID: 2523562]
[42]
Chevaliez, S.; Pawlotsky, J-M. HCV genome and life cycle. In: Hepatitis C Viruses: Genomes and Molecular Biology; Horizon Bioscience: Norfolk (UK), 2006.
[43]
Otto, G.A.; Puglisi, J.D. The pathway of HCV IRES-mediated translation initiation. Cell, 2004, 119(3), 369-380.
[http://dx.doi.org/10.1016/j.cell.2004.09.038] [PMID: 15507208]
[44]
Romero-López, C.; Ríos-Marco, P.; Berzal-Herranz, B.; Berzal-Herranz, A. The HCV genome domains 5BSL3.1 and 5BSL3.3 act as managers of translation. Sci. Rep., 2018, 8(1), 16101.
[http://dx.doi.org/10.1038/s41598-018-34422-7] [PMID: 30382192]
[45]
Kim, J.L.; Morgenstern, K.A.; Lin, C.; Fox, T.; Dwyer, M.D.; Landro, J.A.; Chambers, S.P.; Markland, W.; Lepre, C.A.; O’Malley, E.T.; Harbeson, S.L.; Rice, C.M.; Murcko, M.A.; Caron, P.R.; Thomson, J.A. Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell, 1996, 87(2), 343-355.
[http://dx.doi.org/10.1016/S0092-8674(00)81351-3] [PMID: 8861917]
[46]
Horwitz, J.A.; Dorner, M.; Friling, T.; Donovan, B.M.; Vogt, A.; Loureiro, J.; Oh, T.; Rice, C.M.; Ploss, A. Expression of heterologous proteins flanked by NS3-4A cleavage sites within the hepatitis C virus polyprotein. Virology, 2013, 439(1), 23-33.
[http://dx.doi.org/10.1016/j.virol.2013.01.019] [PMID: 23485372]
[47]
Shiryaev, S.A.; Thomsen, E.R.; Cieplak, P.; Chudin, E.; Cheltsov, A.V.; Chee, M.S.; Kozlov, I.A.; Strongin, A.Y. New details of HCV NS3/4A proteinase functionality revealed by a high-throughput cleavage assay. PLoS One, 2012, 7(4), e35759.
[http://dx.doi.org/10.1371/journal.pone.0035759] [PMID: 22558217]
[48]
Landro, J.A.; Raybuck, S.A.; Luong, Y.P.C.; O’Malley, E.T.; Harbeson, S.L.; Morgenstern, K.A.; Rao, G.; Livingston, D.J. Mechanistic role of an NS4A peptide cofactor with the truncated NS3 protease of hepatitis C virus: Elucidation of the NS4A stimulatory effect via kinetic analysis and inhibitor mapping. Biochemistry, 1997, 36(31), 9340-9348.
[http://dx.doi.org/10.1021/bi963054n] [PMID: 9235976]
[49]
Kim, D.W.; Gwack, Y.; Han, J.H.; Choe, J. C-terminal domain of the hepatitis C virus NS3 protein contains an RNA helicase activity. Biochem. Biophys. Res. Commun., 1995, 215(1), 160-166.
[http://dx.doi.org/10.1006/bbrc.1995.2447] [PMID: 7575585]
[50]
Wu, J.; Bera, A.K.; Kuhn, R.J.; Smith, J.L. Structure of the Flavivirus helicase: Implications for catalytic activity, protein interactions, and proteolytic processing. J. Virol., 2005, 79(16), 10268-10277.
[http://dx.doi.org/10.1128/JVI.79.16.10268-10277.2005] [PMID: 16051820]
[51]
Egger, D.; Wölk, B.; Gosert, R.; Bianchi, L.; Blum, H.E.; Moradpour, D.; Bienz, K. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex. J. Virol., 2002, 76(12), 5974-5984.
[http://dx.doi.org/10.1128/JVI.76.12.5974-5984.2002] [PMID: 12021330]
[52]
Moradpour, D.; Penin, F. Hepatitis C virus proteins: From structure to function. Curr. Top. Microbiol. Immunol., 2013, 369, 113-142.
[53]
Blight, K.J.; Kolykhalov, A.A.; Rice, C.M. Efficient initiation of HCV RNA replication in cell culture. Science, 2000, 290(5498), 1972-1974.
[http://dx.doi.org/10.1126/science.290.5498.1972] [PMID: 11110665]
[54]
Krieger, N.; Lohmann, V.; Bartenschlager, R. Enhancement of hepatitis C virus RNA replication by cell culture-adaptive mutations. J. Virol., 2001, 75(10), 4614-4624.
[http://dx.doi.org/10.1128/JVI.75.10.4614-4624.2001] [PMID: 11312331]
[55]
Agol, V.I.; Gmyl, A.P. Emergency services of viral RNAs: Repair and remodeling. Microbiol. Mol. Biol. Rev., 2018, 82(2), e00067-e17.
[http://dx.doi.org/10.1128/MMBR.00067-17] [PMID: 29540453]
[56]
Kumar, D.; Malik, A.; Asim, M.; Chakravarti, A.; Das, R.H.; Kar, P. Influence of quasispecies on virological responses and disease severity in patients with chronic hepatitis C. World J. Gastroenterol., 2008, 14(5), 701-708.
[http://dx.doi.org/10.3748/wjg.14.701] [PMID: 18205258]
[57]
Chambers, T.J.; Fan, X.; Droll, D.A.; Hembrador, E.; Slater, T.; Nickells, M.W.; Dustin, L.B.; DiBisceglie, A.M. Quasispecies heterogeneity within the E1/E2 region as a pretreatment variable during pegylated interferon therapy of chronic hepatitis C virus infection. J. Virol., 2005, 79(5), 3071-3083.
[http://dx.doi.org/10.1128/JVI.79.5.3071-3083.2005] [PMID: 15709027]
[58]
Madani, T.A. Hepatitis C virus infections reported over 11 years of surveillance in Saudi Arabia. Trans. R. Soc. Trop. Med. Hyg., 2009, 103(2), 132-136.
[http://dx.doi.org/10.1016/j.trstmh.2008.08.001] [PMID: 18789464]
[59]
Lavanchy, D. Evolving epidemiology of hepatitis C virus. Clin. Microbiol. Infect., 2011, 17(2), 107-115.
[http://dx.doi.org/10.1111/j.1469-0691.2010.03432.x] [PMID: 21091831]
[60]
Al-Faleh, F.Z.; Huraib, S.; Sbeih, F.; Al-Karawi, M.; Al-Rashed, R.; Al-Mofleh, I.A.; Sougiyyah, M.; Shaheen, M.; Ramia, S. Hepatitis C virus genotypes in patients with chronic liver disease and haemodialysis patients from Saudi Arabia. J. Viral Hepat., 1995, 2(6), 293-296.
[http://dx.doi.org/10.1111/j.1365-2893.1995.tb00044.x] [PMID: 8732175]
[61]
Osoba, A.O. Hepatitis C virus genotypes in Saudi Arabia. Saudi Med. J., 2002, 23(1), 7-12.
[PMID: 11938356]
[62]
Fakeeh, M.; Zaki, A.M.; Hepatitis, C. Prevalence and common genotypes among ethnic groups in Jeddah, Saudi Arabia. Am. J. Trop. Med. Hyg., 1999, 61(6), 889-892.
[http://dx.doi.org/10.4269/ajtmh.1999.61.889] [PMID: 10674665]
[63]
Al Traif, I.; Al Balwi, M.A.; Abdulkarim, I.; Handoo, F.A.; Alqhamdi, H.S.; Alotaibi, M.; Aljumah, A.; Al Ashqar, H.I.; Bzeizi, K.; Al Quaiz, M.; Alalwan, A.; Al Hamoudi, W.; Alswat, K.; Sanai, F.; Abdo, A. HCV genotypes among 1013 Saudi nationals: A multicenter study. Ann. Saudi Med., 2013, 33(1), 10-12.
[http://dx.doi.org/10.5144/0256-4947.2013.10] [PMID: 23458933]
[64]
Khan, A.; Al Balwi, M.; AlAyyar, L.; AlAbdulkareem, I.; Albekairy, A.; Aljumah, A. Tracing the epidemic history of hepatitis C virus genotypes in Saudi Arabia. Infect. Genet. Evol., 2017, 52, 82-88.
[http://dx.doi.org/10.1016/j.meegid.2017.04.024] [PMID: 28458032]
[65]
Bosmans, J.L.; Nouwen, E.J.; Behets, G.; Gorteman, K.; Huraib, S.O.; Shaheen, F.A.; Maertens, G.; Verpooten, G.A.; Elseviers, M.M.; de Broe, M.E. Prevalence and clinical expression of HCV-genotypes in haemodialysis-patients of two geographically remote countries: Belgium and Saudi-Arabia. Clin. Nephrol., 1997, 47(4), 256-262.
[PMID: 9128793]
[66]
Qadi, A.A.; Tamim, H.; Ameen, G.; Bu-Ali, A.; Al-Arrayed, S.; Fawaz, N.A.; Almawi, W.Y. Hepatitis B and hepatitis C virus prevalence among dialysis patients in Bahrain and Saudi Arabia: A survey by serologic and molecular methods. Am. J. Infect. Control, 2004, 32(8), 493-495.
[http://dx.doi.org/10.1016/j.ajic.2003.12.009] [PMID: 15573057]
[67]
Akbar, H.O. Hepatitis C virus infection in Saudi Arabia. Saudi J. Gastroenterol., 2004, 10(3), 127-131.
[PMID: 19861835]
[68]
Farag, M.M.; Sofy, A.R.; Mousa, A.A.; Ahmed, M.A.; Alganzory, M.R. Molecular assay and genotyping of hepatitis C virus among infected Egyptian and Saudi Arabian patients. Virology, 2015, 6, 1-10.
[http://dx.doi.org/10.4137/VRT.S32016]
[69]
Al Zayed, R.M.; Hamdy, N.M.; Al-Ajlan, H.H.; Aref, N.M. Prevalence of HCV genotypes and viral load in Saudi Arabia. Int. J. Integr. Med, 2015, 4(2), 26-41.
[70]
Ashgar, A.H.I.; Khan, M.Q.; Ahdal, A.M.; Thawadi, A.S.; Helmy, A.S.; Qahtani, A.A.; Sanai, F.M. Hepatitis C genotype 4: Genotypic diversity, epidemiological profile, and clinical relevance of subtypes in Saudi Arabia. Saudi J. Gastroenterol., 2013, 19(1), 28.
[71]
Moneim, A.A.S.; Bamaga, M.S.; Shehab, G.M.G.; Elsaad, A.A.A.S.A.; Farahat, F.M. HCV infection among Saudi population: High prevalence of genotype 4 and increased viral clearance rate. PLoS One, 2012, 7(1), e29781.
[http://dx.doi.org/10.1371/journal.pone.0029781] [PMID: 22253780]
[72]
Shobokshi, O.A.; Serebour, F.E.; Skakni, L.I. Hepatitis C genotypes/subtypes among chronic hepatitis patients in Saudi Arabia. Saudi Med. J., 2003, 24(S2), S87-S91.
[PMID: 12897908]
[73]
Mohamoud, Y.A.; Riome, S.; Abu-Raddad, L.J. Epidemiology of hepatitis C virus in the Arabian Gulf countries: Systematic review and meta-analysis of prevalence. Int. J. Infect. Dis., 2016, 46, 116-125.
[http://dx.doi.org/10.1016/j.ijid.2016.03.012] [PMID: 26996460]
[74]
Thong, V.D.; Akkarathamrongsin, S.; Poovorawan, K.; Tangkijvanich, P.; Poovorawan, Y. Hepatitis C virus genotype 6: Virology, epidemiology, genetic variation and clinical implication. World J. Gastroenterol., 2014, 20(11), 2927-2940.
[http://dx.doi.org/10.3748/wjg.v20.i11.2927] [PMID: 24659883]
[75]
Marie, M.A.M. Genotyping of hepatitis C virus (HCV) in infected patients from Saudi Arabia. Afr. J. Microbiol. Res., 2011, 5(16), 2388-2390.
[76]
Ghaderi-Zefrehi, H.; Gholami-Fesharaki, M.; Sharafi, H.; Sadeghi, F.; Alavian, S.M. The distribution of hepatitis C virus genotypes in middle eastern countries: A systematic review and meta-analysis. Hepat. Mon., 2016, 16(9), e40357.
[http://dx.doi.org/10.5812/hepatmon.40357] [PMID: 27826320]
[77]
Abdo, A.A.; Sanai, F.M.; Al-Faleh, F.Z. Epidemiology of viral hepatitis in Saudi Arabia: Are we off the hook? Saudi J. Gastroenterol., 2012, 18(6), 349.
[78]
Halawani, M.R. Dermatological manifestations of hepatitis C virus infection in Saudi Arabia. Saudi Med. J., 2014, 35(6), 531-537.
[PMID: 24888650]
[79]
Kohara, T.K.; Kohara, M. Hepatitis C virus: Viral quasispecies and genotypes. Int. J. Mol. Sci., 2017, 19(1), 23.
[http://dx.doi.org/10.3390/ijms19010023] [PMID: 29271914]
[80]
Al-Knawy, B.; Okamoto, H.; Mekki, A.E.A.; Khalafalla, E.M.; Al Wabel, A.; Qazi, F.; Khan, A.; Shatoor, A. Distribution of hepatitis C genotype and co-infection rate with hepatitis G in Saudi Arabia. Hepatol. Res., 2002, 24(2), 95-98.
[http://dx.doi.org/10.1016/S1386-6346(02)00080-3] [PMID: 12270737]
[81]
Hathorn, E.; Elsharkawy, A.M. Management of hepatitis C genotype 4 in the directly acting antivirals era. BMJ Open Gastroenterol., 2016, 3(1), e000112.
[http://dx.doi.org/10.1136/bmjgast-2016-000112] [PMID: 27752338]
[82]
Manns, M.P.; McHutchison, J.G.; Gordon, S.C.; Rustgi, V.K.; Shiffman, M.; Reindollar, R.; Goodman, Z.D.; Koury, K.; Ling, M.H.; Albrecht, J.K. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: A randomised trial. Lancet, 2001, 358(9286), 958-965.
[http://dx.doi.org/10.1016/S0140-6736(01)06102-5] [PMID: 11583749]
[83]
Strader, D.B.; Wright, T.; Thomas, D.L.; Seeff, L.B. Diagnosis, management, and treatment of hepatitis C. Hepatology, 2004, 39(4), 1147-1171.
[http://dx.doi.org/10.1002/hep.20119] [PMID: 15057920]
[84]
Lebray, P.; Nalpas, B.; Pichard, V.A.; Broissand, C.; Sobesky, R.; Serpaggi, J.; Fontaine, H.; Pol, S. The impact of haematopoietic growth factors on the management and efficacy of antiviral treatment in patients with hepatitis C virus. Antivir. Ther., 2005, 10(6), 769-776.
[http://dx.doi.org/10.1177/135965350501000605] [PMID: 16218177]
[85]
Schaefer, M.; Schmidt, F.; Folwaczny, C.; Lorenz, R.; Martin, G.; Schindlbeck, N.; Heldwein, W.; Soyka, M.; Grunze, H.; Koenig, A.; Loeschke, K. Adherence and mental side effects during hepatitis C treatment with interferon alfa and ribavirin in psychiatric risk groups. Hepatology, 2003, 37(2), 443-451.
[http://dx.doi.org/10.1053/jhep.2003.50031] [PMID: 12540795]
[86]
Toniutto, P.; Fabris, C.; Fumo, E.; Apollonio, L.; Caldato, M.; Avellini, C.; Minisini, R.; Pirisi, M. Pegylated versus standard interferon-α in antiviral regimens for post-transplant recurrent hepatitis C: Comparison of tolerability and efficacy. J. Gastroenterol. Hepatol., 2005, 20(4), 577-582.
[http://dx.doi.org/10.1111/j.1440-1746.2005.03795.x] [PMID: 15836706]
[87]
Araújo, A.R.; Peruhype-Magalhães, V.; Coelho-dos-Reis, J.G.A.; Chaves, L.P.V.; Lima, T.A.; Pimentel, J.P.D.; de Paula, L.; Almeida, C.M.; Tarragô, A.M.; Tateno, A.; Levi, J.E.; Teixeira-Carvalho, A.; Martins-Filho, O.A.; Lira, E.F.; Torres, K.L.; Talhari, S.; Malheiro, A. Dual role of IL-12 in the therapeutic efficacy or failure during combined PEG-Interferon-α2A and ribavirin therapy in patients with chronic hepatitis C. Immunol. Lett., 2013, 154(1-2), 61-69.
[http://dx.doi.org/10.1016/j.imlet.2013.07.010] [PMID: 23973662]
[88]
Hadziyannis, S.J.; Sette, H., Jr; Morgan, T.R.; Balan, V.; Diago, M.; Marcellin, P.; Ramadori, G.; Bodenheimer, H., Jr; Bernstein, D.; Rizzetto, M.; Zeuzem, S.; Pockros, P.J.; Lin, A.; Ackrill, A.M. Peginterferon-α2a and ribavirin combination therapy in chronic hepatitis C: A randomized study of treatment duration and ribavirin dose. Ann. Intern. Med., 2004, 140(5), 346-355.
[http://dx.doi.org/10.7326/0003-4819-140-5-200403020-00010] [PMID: 14996676]
[89]
Geddawy, A.; Ibrahim, Y.F.; Elbahie, N.M.; Ibrahim, M.A. Direct acting anti-hepatitis C virus drugs: Clinical pharmacology and future direction. J. Transl. Int. Med., 2017, 5(1), 8-17.
[http://dx.doi.org/10.1515/jtim-2017-0007] [PMID: 28680834]
[90]
Lok, S.F.A. HCV NS5A inhibitors in development. Clin. Liver Dis., 2013, 17(1), 111-121.
[http://dx.doi.org/10.1016/j.cld.2012.09.006] [PMID: 23177287]
[91]
Asselah, T.; Marcellin, P.; Schinazi, R.F. Treatment of hepatitis C virus infection with direct-acting antiviral agents: 100% cure? Liver Int., 2018, 38(S1), 7-13.
[http://dx.doi.org/10.1111/liv.13673] [PMID: 29427484]
[92]
De Clercq, E. Current race in the development of DAAs (direct-acting antivirals) against HCV. Biochem. Pharmacol., 2014, 89(4), 441-452.
[http://dx.doi.org/10.1016/j.bcp.2014.04.005] [PMID: 24735613]
[93]
Asselah, T.; Boyer, N.; Saadoun, D.; Peignoux, M.M.; Marcellin, P. Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN -free treatment and future perspectives. Liver Int., 2016, 36(S1), 47-57.
[http://dx.doi.org/10.1111/liv.13027] [PMID: 26725897]
[94]
Cheng, G.; Yu, M.; Peng, B.; Lee, Y.J.; Martin, T.A.; Gong, R.; Bush, C.; Worth, A.; Nash, M.; Chan, K.; Yang, H.; Beran, R.; Tian, Y.; Perry, J.; Taylor, J.; Yang, C.; Paulson, M.; Delaney, W.; Link, J.O. 1191 GS-5816, A second generation HCV NS5A inhibitor with potent antiviral activity, broad genotypic coverage and a high resistance barrier. J. Hepatol., 2013, 58(S1), S484-S485.
[http://dx.doi.org/10.1016/S0168-8278(13)61192-7]
[95]
Curry, M.P.; O’Leary, J.G.; Bzowej, N.; Muir, A.J.; Korenblat, K.M.; Fenkel, J.M.; Reddy, K.R.; Lawitz, E.; Flamm, S.L.; Schiano, T.; Teperman, L.; Fontana, R.; Schiff, E.; Fried, M.; Doehle, B.; An, D.; McNally, J.; Osinusi, A.; Brainard, D.M.; McHutchison, J.G.; Brown, R.S., Jr; Charlton, M. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N. Engl. J. Med., 2015, 373(27), 2618-2628.
[http://dx.doi.org/10.1056/NEJMoa1512614] [PMID: 26569658]
[96]
Jacobson, I.M.; Lawitz, E.; Gane, E.J.; Willems, B.E.; Ruane, P.J.; Nahass, R.G.; Borgia, S.M.; Shafran, S.D.; Workowski, K.A.; Pearlman, B.; Hyland, R.H.; Stamm, L.M.; Svarovskaia, E.; Dvory-Sobol, H.; Zhu, Y.; Subramanian, G.M.; Brainard, D.M.; McHutchison, J.G.; Bräu, N.; Berg, T.; Agarwal, K.; Bhandari, B.R.; Davis, M.; Feld, J.J.; Dore, G.J.; Stedman, C.A.M.; Thompson, A.J.; Asselah, T.; Roberts, S.K.; Foster, G.R. Efficacy of 8 weeks of sofosbuvir, velpatasvir, and voxilaprevir in patients with chronic HCV infection: 2 phase 3 randomized trials. Gastroenterology, 2017, 153(1), 113-122.
[http://dx.doi.org/10.1053/j.gastro.2017.03.047] [PMID: 28390869]
[97]
Ng, T.I.; Krishnan, P.; Pilot-Matias, T.; Kati, W.; Schnell, G.; Beyer, J.; Reisch, T.; Lu, L.; Dekhtyar, T.; Irvin, M.; Tripathi, R.; Maring, C.; Randolph, J.T.; Wagner, R.; Collins, C. In vitro antiviral activity and resistance profile of the next-generation hepatitis C virus NS5A inhibitor pibrentasvir. Antimicrob. Agents Chemother., 2017, 61(5), e02558-e16.
[http://dx.doi.org/10.1128/AAC.02558-16] [PMID: 28193664]
[98]
Zeuzem, S.; Foster, G.; Wang, S. 8-or 12-week glecaprevir/pibrentasvir in non-cirrhotic HCV genotype 1 or 3. N. Engl. J. Med., 2018, 378(4), 354-369.
[http://dx.doi.org/10.1056/NEJMoa1702417] [PMID: 29365309]
[99]
Zeuzem, S.; Ghalib, R.; Reddy, K.R.; Pockros, P.J.; Ari, Z.B.; Zhao, Y.; Brown, D.D.; Wan, S.; DiNubile, M.J.; Nguyen, B.Y.; Robertson, M.N.; Wahl, J.; Barr, E.; Butterton, J.R. Grazoprevir–elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection: A randomized trial. Ann. Intern. Med., 2015, 163(1), 1-13.
[http://dx.doi.org/10.7326/M15-0785] [PMID: 25909356]
[100]
Andreone, P.; Colombo, M.G.; Enejosa, J.V.; Koksal, I.; Ferenci, P.; Maieron, A.; Müllhaupt, B.; Horsmans, Y.; Weiland, O.; Reesink, H.W. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology., 2014, 147(2), 359-365. e351.
[101]
Schinazi, R.; Halfon, P.; Marcellin, P.; Asselah, T. HCV direct-acting antiviral agents: The best interferon-free combinations. Liver Int., 2014, 34(S1), 69-78.
[http://dx.doi.org/10.1111/liv.12423] [PMID: 24373081]
[102]
Sulkowski, M.S.; Jacobson, I.M.; Nelson, D.R. Daclatasvir plus sofosbuvir for HCV infection. N. Engl. J. Med., 2014, 370(16), 1560-1561.
[http://dx.doi.org/10.1056/NEJMc1401726] [PMID: 24738674]
[103]
Kish, T.; Aziz, A.; Sorio, M. Hepatitis C in a new era: A review of current therapies. P&T, 2017, 42(5), 316-329.
[PMID: 28479841]
[104]
Lenz, O.; Verbinnen, T.; Lin, T.I.; Vijgen, L.; Cummings, M.D.; Lindberg, J.; Berke, J.M.; Dehertogh, P.; Fransen, E.; Scholliers, A.; Vermeiren, K.; Ivens, T.; Raboisson, P.; Edlund, M.; Storm, S.; Vrang, L.; de Kock, H.; Fanning, G.C.; Simmen, K.A. In vitro resistance profile of the hepatitis C virus NS3/4A protease inhibitor TMC435. Antimicrob. Agents Chemother., 2010, 54(5), 1878-1887.
[http://dx.doi.org/10.1128/AAC.01452-09] [PMID: 20176898]
[105]
Kieffer, T.L.; De Meyer, S.; Bartels, D.J.; Sullivan, J.C.; Zhang, E.Z.; Tigges, A.; Dierynck, I.; Spanks, J.; Dorrian, J.; Jiang, M.; Adiwijaya, B.; Ghys, A.; Beumont, M.; Kauffman, R.S.; Adda, N.; Jacobson, I.M.; Sherman, K.E.; Zeuzem, S.; Kwong, A.D.; Picchio, G. Hepatitis C viral evolution in genotype 1 treatment-naïve and treatment-experienced patients receiving telaprevir-based therapy in clinical trials. PLoS One, 2012, 7(4), e34372.
[http://dx.doi.org/10.1371/journal.pone.0034372] [PMID: 22511937]
[106]
Aguiar, B.F.; Campos, G.R.F.; Rodrigues, J.P.V.; Marques, N.N.; Molina, B.F.; Bittar, C.; Souza, F.F.; Martinelli, A.L.C.; Rahal, P.; Pereira, L.R.L. Baseline resistance associated substitutions in HCV genotype 1 infected cohort treated with Simeprevir, Daclatasvir and Sofosbuvir in Brazil. Clin. Res. Hepatol. Gastroenterol., 2020, 44(3), 329-339.
[http://dx.doi.org/10.1016/j.clinre.2019.07.015] [PMID: 31523019]
[107]
Gao, M.; Nettles, R.E.; Belema, M.; Snyder, L.B.; Nguyen, V.N.; Fridell, R.A.; Serrano-Wu, M.H.; Langley, D.R.; Sun, J.H.; O’Boyle, D.R., II; Lemm, J.A.; Wang, C.; Knipe, J.O.; Chien, C.; Colonno, R.J.; Grasela, D.M.; Meanwell, N.A.; Hamann, L.G. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature, 2010, 465(7294), 96-100.
[http://dx.doi.org/10.1038/nature08960] [PMID: 20410884]
[108]
Fridell, R.A.; Qiu, D.; Wang, C.; Valera, L.; Gao, M. Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system. Antimicrob. Agents Chemother., 2010, 54(9), 3641-3650.
[http://dx.doi.org/10.1128/AAC.00556-10] [PMID: 20585111]
[109]
Costa, V.D.; Delvaux, N.; Mello, B.C.E.; Nunes, E.P.; de Sousa, P.S.F.; de Rodrigues, S.L.L.L.X.; Lampe, E.; do Mello, A.F.C. Prevalence of baseline NS3 resistance-associated substitutions (RASs) on treatment with protease inhibitors in patients infected with HCV genotype 1. Clin. Res. Hepatol. Gastroenterol., 2019, 43(6), 700-706.
[http://dx.doi.org/10.1016/j.clinre.2019.02.009] [PMID: 30880098]
[110]
Flint, M.; Mullen, S.; Deatly, A.M.; Chen, W.; Miller, L.Z.; Ralston, R.; Broom, C.; Emini, E.A.; Howe, A.Y.M. Selection and characterization of hepatitis C virus replicons dually resistant to the polymerase and protease inhibitors HCV-796 and boceprevir (SCH 503034). Antimicrob. Agents Chemother., 2009, 53(2), 401-411.
[http://dx.doi.org/10.1128/AAC.01081-08] [PMID: 18936191]
[111]
Soumana, D.I.; Ali, A.; Schiffer, C.A. Structural analysis of asunaprevir resistance in HCV NS3/4A protease. ACS Chem. Biol., 2014, 9(11), 2485-2490.
[http://dx.doi.org/10.1021/cb5006118] [PMID: 25243902]
[112]
McPhee, F.; Friborg, J.; Levine, S.; Chen, C.; Falk, P.; Yu, F.; Hernandez, D.; Lee, M.S.; Chaniewski, S.; Sheaffer, A.K.; Pasquinelli, C. Resistance analysis of the hepatitis C virus NS3 protease inhibitor asunaprevir. Antimicrob. Agents Chemother., 2012, 56(7), 3670-3681.
[http://dx.doi.org/10.1128/AAC.00308-12] [PMID: 22508297]
[113]
Tong, X.; Chase, R.; Skelton, A.; Chen, T.; Wrightminogue, J.; Malcolm, B. Identification and analysis of fitness of resistance mutations against the HCV protease inhibitor SCH 503034. Antiviral Res., 2006, 70(2), 28-38.
[http://dx.doi.org/10.1016/j.antiviral.2005.12.003] [PMID: 16448708]
[114]
Walker, A.; Filke, S.; Lübke, N.; Obermeier, M.; Kaiser, R.; Häussinger, D.; Timm, J.; Bock, H.H. Detection of a genetic footprint of the sofosbuvir resistance-associated substitution S282T after HCV treatment failure. Virol. J., 2017, 14(1), 106.
[http://dx.doi.org/10.1186/s12985-017-0779-4] [PMID: 28595606]
[115]
Vallet, S.; Viron, F.; Henquell, C.; Le Guillemette, G.H.; Lagathu, G.; Abravanel, F.; Trimoulet, P.; Soussan, P.; Schvoerer, E.; Rosenberg, A.; Gouriou, S.; Colson, P.; Izopet, J.; Payan, C. NS3 protease polymorphism and natural resistance to protease inhibitors in French patients infected with HCV genotypes 1-5. Antivir. Ther., 2011, 16(7), 1093-1102.
[http://dx.doi.org/10.3851/IMP1900] [PMID: 22024525]
[116]
Morsica, G.; Andolina, A.; Merli, M.; Messina, E.; Hasson, H.; Lazzarin, A.; Foppa, U.C.; Bagaglio, S. NS3 protease resistance-associated substitutions in liver tissue and plasma samples from patients infected by hepatitis C virus genotype 1A or 1B. Arch. Virol., 2017, 162(8), 2271-2277.
[http://dx.doi.org/10.1007/s00705-017-3341-1] [PMID: 28421367]
[117]
Paolucci, S.; Fiorina, L.; Mariani, B.; Gulminetti, R.; Novati, S.; Barbarini, G.; Bruno, R.; Baldanti, F. Naturally occurring resistance mutations to inhibitors of HCV NS5A region and NS5B polymerase in DAA treatment-naïve patients. Virol. J., 2013, 10(1), 355.
[http://dx.doi.org/10.1186/1743-422X-10-355] [PMID: 24341898]
[118]
Martínez, A.P.; Culasso, A.C.A.; Pérez, P.S.; Romano, V.; Campos, R.H.; Ridruejo, E.; García, G.; Di Lello, F.A. Polymorphisms associated with resistance to protease inhibitors in naïve patients infected with hepatitis C virus genotype 1 in Argentina: Low prevalence of Q80K. Virus Res., 2017, 240, 140-146.
[http://dx.doi.org/10.1016/j.virusres.2017.08.006] [PMID: 28837817]
[119]
Sarrazin, C.; Sobol, D.H.; Svarovskaia, E.S.; Doehle, B.P.; Pang, P.S.; Chuang, S.M.; Ma, J.; Ding, X.; Afdhal, N.H.; Kowdley, K.V. Prevalence of resistance-associated substitutions in HCV NS5A, NS5B, or NS3 and outcomes of treatment with ledipasvir and sofosbuvir. Gastroenterology., 2016, 151(3), 501-512. e501.
[120]
Arias, A.; Aguilera, A.; Soriano, V.; Gutiérrez, B.L.; Lledó, G.; Navarro, D.; Treviño, A.; Otero, E.; Peña, J.M.; Mons, C.V.; de Mendoza, C. Rate and predictors of treatment failure to all-oral HCV regimens outside clinical trials. Antivir. Ther., 2017, 22(4), 307-312.
[http://dx.doi.org/10.3851/IMP3061] [PMID: 27341294]
[121]
Michaluk, Z.D.; Jaroszewicz, J.; Buczyńska, I.; Simon, K.; Lorenc, B.; Zdunek, T.M.; Tomasiewicz, K.; Sitko, M.; Garlicki, A.; Janczewska, E.; Dybowska, D.; Halota, W.; Pawłowska, M.; Pabjan, P.; Mazur, W.; Andrzejuk, C.A.; Berak, H.; Horban, A.; Socha, Ł.; Klapaczyński, J.; Piekarska, A.; Blaszkowska, M.; Wdowik, B.T.; Dobracka, B.; Tronina, O.; Deroń, Z.; Warzecha, B.J.; Laurans, Ł.; Flisiak, R. Real-world experience with Grazoprevir/Elbasvir in the treatment of previously “difficult to treat” patients infected with hepatitis C virus genotype 1 and 4. J. Gastroenterol. Hepatol., 2020, 35(7), 1238-1246.
[http://dx.doi.org/10.1111/jgh.14936] [PMID: 31734959]
[122]
El-Khayat, H.; Fouad, Y.; Mohamed, H.I.; El-Amin, H.; Kamal, E.M.; Maher, M.; Risk, A. Sofosbuvir plus daclatasvir with or without ribavirin in 551 patients with hepatitis C-related cirrhosis, genotype 4. Aliment. Pharmacol. Ther., 2018, 47(5), 674-679.
[http://dx.doi.org/10.1111/apt.14482] [PMID: 29314146]
[123]
Ahmed, O.A.; Elsebaey, M.A.; Fouad, M.H.A.; Elashry, H.; Elshafie, A.I.; Elhadidy, A.A.; Esheba, N.E.; Elnaggar, M.H.; Soliman, S.; Abd-Elsalam, S. Outcomes and predictors of treatment response with sofosbuvir plus daclatasvir with or without ribavirin in Egyptian patients with genotype 4 hepatitis C virus infection. Infect. Drug Resist., 2018, 11, 441-445.
[http://dx.doi.org/10.2147/IDR.S160593] [PMID: 29628768]
[124]
De Francesco, M.A.; Gargiulo, F.; Zaltron, S.; Spinetti, A.; Castelli, F.; Caruso, A. DAA treatment failure in a HIV/HBV/HCV co-infected patient carrying a chimeric HCV genotype 4/1b. Int. J. Environ. Res. Public Health, 2022, 19(18), 11655.
[http://dx.doi.org/10.3390/ijerph191811655] [PMID: 36141921]
[125]
Fourati, S.; Rodriguez, C.; Hézode, C.; Soulier, A.; Ruiz, I.; Poiteau, L.; Chevaliez, S.; Pawlotsky, J.M. Frequent antiviral treatment failures in patients infected with hepatitis C virus genotype 4, subtype 4r. Hepatology, 2019, 69(2), 513-523.
[http://dx.doi.org/10.1002/hep.30225] [PMID: 30125371]
[126]
Ferenci, P. Treatment of hepatitis C in difficult-to-treat patients. Nat. Rev. Gastroenterol. Hepatol., 2015, 12(5), 284-292.
[http://dx.doi.org/10.1038/nrgastro.2015.53] [PMID: 25895822]
[127]
Sarrazin, C.; Cooper, C.L.; Manns, M.P.; Reddy, K.R.; Kowdley, K.V.; Roberts, S.K.; Dvory-Sobol, H.; Svarovskia, E.; Martin, R.; Camus, G.; Doehle, B.P.; Stamm, L.M.; Hyland, R.H.; Brainard, D.M.; Mo, H.; Gordon, S.C.; Bourliere, M.; Zeuzem, S.; Flamm, S.L. No impact of resistance-associated substitutions on the efficacy of sofosbuvir, velpatasvir, and voxilaprevir for 12 weeks in HCV DAA-experienced patients. J. Hepatol., 2018, 69(6), 1221-1230.
[http://dx.doi.org/10.1016/j.jhep.2018.07.023] [PMID: 30098373]
[128]
Nejabat, N.; Hosseini, S.Y.; Sarvari, J.; Gorzin, A.A.; Fattahi, M.R.; Rasoolian, M. The investigation of drug resistance substitutions in NS3 protease sequence of hepatitis C virus from non-responder patients. Asian Pac. J. Cancer Prev., 2019, 20(8), 2311-2317.
[http://dx.doi.org/10.31557/APJCP.2019.20.8.2311] [PMID: 31450900]
[129]
Zeuzem, S.; Mizokami, M.; Pianko, S.; Mangia, A.; Han, K.H.; Martin, R.; Svarovskaia, E.; Dvory-Sobol, H.; Doehle, B.; Hedskog, C.; Yun, C.; Brainard, D.M.; Knox, S.; McHutchison, J.G.; Miller, M.D.; Mo, H.; Chuang, W.L.; Jacobson, I.; Dore, G.J.; Sulkowski, M. NS5A resistance-associated substitutions in patients with genotype 1 hepatitis C virus: Prevalence and effect on treatment outcome. J. Hepatol., 2017, 66(5), 910-918.
[http://dx.doi.org/10.1016/j.jhep.2017.01.007] [PMID: 28108232]
[130]
Bertoli, A.; Sorbo, M.C.; Aragri, M.; Lenci, I.; Teti, E.; Polilli, E.; Di Maio, V.C.; Gianserra, L.; Biliotti, E.; Masetti, C.; Magni, C.F.; Babudieri, S.; Nicolini, L.A.; Milana, M.; Cacciatore, P.; Sarmati, L.; Pellicelli, A.; Paolucci, S.; Craxì, A.; Morisco, F.; Palitti, V.P.; Siciliano, M.; Coppola, N.; Iapadre, N.; Puoti, M.; Rizzardini, G.; Taliani, G.; Pasquazzi, C.; Andreoni, M.; Parruti, G.; Angelico, M.; Perno, C.F.; Cento, V.; Silberstein, C.F.; Andreone, P.; Baldanti, F.; Barbarini, G.; Boccaccio, V.; Boglione, L.; Bolis, M.; Bonora, S.; Borghi, V.; Brancaccio, G.; Bruno, S.; Bruzzone, B.; Calvaruso, V.; Caporaso, N.; Ciaccio, A.; Ciancio, A.; Colombatto, P.; Cozzolongo, R.; D’Ambrosio, C.; D’Ettorre, G.; De Leonardis, F.; De Luca, A.; Di Biagio, A.; Di Perri, G.; Francioso, S.; Gaeta, G.B.; Gasbarrini, A.; Ghisetti, V.; Giorgini, A.; Grieco, A.; Gubertini, G.; Gulminetti, R.; Lambiase, L.; Landonio, S.; Lichtner, M.; Maida, I.; Marenco, S.; Marinaro, L.; Maserati, R.; Melis, M.; Menzaghi, B.; Meregalli, E.; Micheli, V.; Niero, F.; Paoloni, M.; Pieri, A.; Rendina, M.; Romagnoli, D.; Rossetti, B.; Ruggiero, T.; Sangiovanni, V.; Starace, M.; Sticchi, L.; Tarquini, P.; Toniutto, P.; Vullo, V.; Zazzi, M. Prevalence of single and multiple natural NS3, NS5A and NS5B resistance-associated substitutions in hepatitis C virus genotypes 1–4 in Italy. Sci. Rep., 2018, 8(1), 8988.
[http://dx.doi.org/10.1038/s41598-018-26862-y] [PMID: 29895871]
[131]
Wei, L.; Omata, M.; Lim, Y.S.; Xie, Q.; Hou, J.L.; Jia, J.; Hedskog, C.; Martin, R.; Doehle, B.; Yang, J.; De-Oertel, S.; Massetto, B.; Kersey, K.; Brainard, D.M.; Svarovskaia, E.; Mo, H.; Han, K.H.; Mizokami, M.; Duan, Z. HCV phylogenetic signature and prevalence of pretreatment NS5A and NS5B NI-Resistance associated substitutions in HCV-Infected patients in Mainland China. Antiviral Res., 2018, 158, 178-184.
[http://dx.doi.org/10.1016/j.antiviral.2018.08.001] [PMID: 30120954]
[132]
Jiang, M.; Mani, N.; Lin, C.; Ardzinski, A.; Nelson, M.; Reagan, D.; Bartels, D.; Zhou, Y.; Nicolas, O.; Rao, B.G.; Müh, U.; Hanzelka, B.; Tigges, A.; Rijnbrand, R.; Kieffer, T.L. In vitro phenotypic characterization of hepatitis C virus NS3 protease variants observed in clinical studies of telaprevir. Antimicrob. Agents Chemother., 2013, 57(12), 6236-6245.
[http://dx.doi.org/10.1128/AAC.01578-13] [PMID: 24100495]
[133]
Anagnostou, O.; Manolakopoulos, S.; Bakoyannis, G.; Papatheodoridis, G.; Zisouli, A.; Gigi, R.M.; Manesis, E.; Ketikoglou, I.; Dalekos, G.; Gogos, C.; Vassiliadis, T.; Tzourmakliotis, D.; Karatapanis, S.; Kanatakis, S. Zoumpoulis; Hounta, A.; Koutsounas, S.; Giannoulis, G.; Tassopoulos, N.; Touloumi, G. Genotype 4 HCV infection is difficult to cure with pegylated interferon and ribavirin. Results from a greek nationwide cohort study. Hippokratia, 2014, 18(1), 57-64.
[PMID: 25125954]
[134]
Brzdęk, M.; Dobrowolska, K.; Flisiak, R.; Zarębska-Michaluk, D. Genotype 4 hepatitis C virus-a review of a diverse genotype. Adv. Med. Sci., 2023, 68(1), 54-59.
[http://dx.doi.org/10.1016/j.advms.2022.12.003] [PMID: 36640687]
[135]
Schnell, G.; Tripathi, R.; Beyer, J.; Reisch, T.; Krishnan, P.; Lu, L.; Dekhtyar, T.; Hall, C.; Vilchez, R.A.; Pilot-Matias, T.; Collins, C. Hepatitis C virus genotype 4 resistance and subtype demographic characterization of patients treated with ombitasvir plus paritaprevir/ritonavir. Antimicrob. Agents Chemother., 2015, 59(11), 6807-6815.
[http://dx.doi.org/10.1128/AAC.01229-15] [PMID: 26282418]
[136]
Mani, N. Clinically relevant HCVdrug resistance mutations figure and tables. Ann Forum Collab HIV Res., 2012, 14(2), 1-10.
[137]
Wyles, D.L.; Luetkemeyer, A.F. Understanding hepatitis C virus drug resistance: Clinical implications for current and future regimens. Top. Antivir. Med., 2017, 25(3), 103-109.
[PMID: 28820725]
[138]
Rahimi, P.; Sharafi, H.; Bahramali, G. SajadianFard, F.; Asadi, N.S.; Alavian, S.M.; Mobarakeh, I.V.; Moravej, S.Z. Prevalence of naturally-occurring NS5A and NS5B resistance-associated substitutions in Iranian patients with chronic hepatitis C infection. Front. Microbiol., 2021, 11, 617375.
[http://dx.doi.org/10.3389/fmicb.2020.617375] [PMID: 33584581]
[139]
Laferrière, M.V.; Dieterich, D.T. GS-7977: A promising nucleotide analog NS5B polymerase inhibitor of HCV. Future Virol., 2012, 7(6), 537-546.
[http://dx.doi.org/10.2217/fvl.12.34]
[140]
Sayan, M.; Yıldırım, F.S.; Akhan, S.; Yıldırım, A.A.; Şirin, G.; Cabalak, M.; Demir, M.; Can, S.; Ersöz, G.; Altıntaş, E.; Ensaroğlu, F.; Akbulut, A.; Şener, A.; Deveci, A. NS5A resistance – associated substitutions in chronic hepatitis C patients with direct acting antiviral treatment failure in Turkey. Int. J. Infect. Dis., 2020, 95, 84-89.
[http://dx.doi.org/10.1016/j.ijid.2020.03.061] [PMID: 32302766]
[141]
Mushtaq, S.; Hashmi, A.H.; Khan, A.; Kazmi, A.R.S.M.; Manzoor, S. Emergence and persistence of resistance-associated substitutions in HCV GT3 patients failing direct-acting antivirals. Front. Pharmacol., 2022, 13, 894460.
[http://dx.doi.org/10.3389/fphar.2022.894460] [PMID: 35571102]
[142]
Atif, M.; Mustaan, M.A.; Falak, S.; Ghaffar, A.; Munir, B. Targeting the effect of sofosbuvir on selective oncogenes expression level of hepatocellular carcinoma Ras/Raf/MEK/ERK pathway in Huh7 cell line. Saudi J. Biol. Sci., 2022, 29(8), 103332.
[http://dx.doi.org/10.1016/j.sjbs.2022.103332] [PMID: 35813116]
[143]
Marascio, N.; Pavia, G.; Strazzulla, A.; Dierckx, T.; Cuypers, L.; Vrancken, B.; Barreca, G.; Mirante, T.; Malanga, D.; Oliveira, D.; Vandamme, A.M.; Torti, C.; Liberto, M.; Focà, A. Detection of natural resistance-associated substitutions by ion semiconductor technology in HCV1b positive, direct-acting antiviral agents-naïve patients. Int. J. Mol. Sci., 2016, 17(9), 1416.
[http://dx.doi.org/10.3390/ijms17091416] [PMID: 27618896]
[144]
Lin, C.; Lin, K.; Luong, Y.P.; Rao, B.G.; Wei, Y.Y.; Brennan, D.L.; Fulghum, J.R.; Hsiao, H.M.; Ma, S.; Maxwell, J.P.; Cottrell, K.M.; Perni, R.B.; Gates, C.A.; Kwong, A.D. In vitro resistance studies of hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061: Structural analysis indicates different resistance mechanisms. J. Biol. Chem., 2004, 279(17), 17508-17514.
[http://dx.doi.org/10.1074/jbc.M313020200] [PMID: 14766754]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy