Hepatitis C virus: Morphogenesis, infection and therapy

doi:10.4254/wjh.v10.i2.186

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World Journal of Hepatology

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1948-5182

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Hepatol. Feb 27, 2018; 10(2): 186-212
Published online Feb 27, 2018. doi: 10.4254/wjh.v10.i2.186

Table 1 Overview of the size of hepatitis C virus proteins

Protein	No. of aa	aa position n ref. seq.	MW of protein, kDa
Core immature	191	1-191	23
Core mature	174	1-174	21
F protein of ARF protein	126-161		Approximately 16-17
E1	192	192-383	35
E2	363	384-746	70
p7	63	747-809	7
NS2	217	810-1026	21
NS3	631	1027-1657	70
NS4A	54	1658-1711	4
NS4B	261	1712-1972	27
NS5A	448	1973-2420	56
NS5B	591	2421-3011	66

No. of aa: Number of amino acid; MW: Molecular weight; kDa: KiloDalton; ref.seq.: Reference sequence (HCV strain H77 ; accession number NC_0041).

Table 2 Commercially available hepatitis C virus RNA detection assays

Assay	Distributor	Technology	Detection limits (IU/mL)	Genotypes	Approval status
Qualitative HCV RNA detection assays
Amplicor^TM HCV 2.0	Roche molecular Systems	PCR	50	All	FDA, CE
Versant^TM HCV	Siemens Medical Solutions Diagnostics	TMA	5-10	All	FDA, CE
Quantitative HCV RNA detection
Amplicor^TM HCV Monitor 2.0	Roche molecular Systems	PCR	500 to approximately 5.10⁵	All	CE
HCV SuperQuant^TM	National Genetics institute	PCR	30 to 10⁷	All	U.S only
Versant^R HCV RNA 3.0	Siemens Medical Solutions Diagnostics	bDNA	615 to 8.10⁶	All	FDA, CE
Cobas^R AmpliPrep/High pure system/Cobas^R TaqMan^R	Roche molecular Systems	Real-time PCR	15 to 10⁷	All	FDA, CE
Abbot RealTime^TM HCV	Abbot Diagnostics	Real-time PCR	10 to 10⁷	All	FDA, CE
Artus HCV QS-RGQ assay	Qiagen	Real-time PCR	34 to 10⁸	All	CE
Versant^RR HCV 1.0 kPCR assay	Siemens	Real-time PCR	10 to approximately 10⁷	-	CE

HCV: hepatitis C virus; TMA: Transcription-mediated amplification of RNA; bDNA: Branched DNA hybridization assay.

Table 3 Selected directly acting antiviral agents and host targeting agents in the pipeline[63]

Drugs name	Company	Target/active site	Phase
NS3/4A protease inhibitors
Vaniprevir (MK-7009)	Merck	Active site/macrocyclic	III
Voxilaprevir GS-9857	Gilead	Active site	III
Glecaprevir (ABT-493)	Abbvie	Active site	III
IDX21437	Idenix	Active site	II
Sovaprevir (ACH-1625)	Achillion	Active site/macrocyclic?	II
Nucleoside analog NS5B polymerase inhibitors (NI)
MK-3682 (formerly IDX20963)	Merck	Active site	II
ACH-3422	Achillion/Janssen	Active site	II
Non- Nucleoside analog NS5B polymerase inhibitors (NNI)
Beclabuvir (BMS-791325)	Bristol-Myers Squib	NNI site 1/Thumb 1	III
Setrobuvir (ANA598)	Anadys/Roche	NNI site 4?/palm 1	II
NS5A inhibitors
BMS-824393	Bristol-Myers Squibb	NS5A protein	II
PPI-461	Presidio	NS5A protein	II
PPI-668	Presidio	NS5A protein	II
Pibrentasvir (ABT-530)	Abbvie	NS5A protein	III
ACH-2928	Achillion	NS5A protein	I
Ruzasvir (MK-8408)	Merck	NS5A protein	II
Host targeting agents
SCY-635	Scynexis	Cyclophilin inhibitor	II
Miravirsen	Santaris	miRNA122 antisense NA	II
RG-101-	Regulus	miRNA122 antisense NA	II
TT-0034	Tacere Therapeutics	RNA interference with HCV	II

Table 4 Selected directly acting antiviral agents and host targeting agents whose development has been stopped or temporarily halted[63]

Drugs name Company Target/Active site
NS3 /4A protease inhibitors
Ciluprevir BILN 2061	Boehringer Ingelheim	Active site/macrocyclic
Narlaprevir (SCH900518)	Schering-Plough	Active site/linear
PHX1766	Pheromix	Active site
Danoprevir (R7227)	Roche/InterMune	Active site/macrocyclic
Faldaprevir (BI201335)	Boehringer Ingelheim	Active site/linear
Telaprevir (VX-950)	Vertex	Withdrawn
Boceprevir (SCH503034)	Merck	Withdrawn
Nucleoside analogue NS5B polymerase inhibitors (NI)
Valopicitabine (NM283)	Idenix/Novartis	Active site
R1626	Roche	Active site
Mericitabine (R7128)	Roche/Pharmasset	Active site
GS-938	Gilead	Active site
IDX184	Idenix	Active site
Non-nucleoside NS5B polymerase inhibitors (NNI)
BILB 1941	Boehringer Ingelheim	NNI site 1/thumb
MK-3281	Merck	NNI site 1/thumb 1
VX-759	Vertex	NNI site 2/thumb 2
VX-222	Vertex	NNI site 2/thumb 2
VX-916	Vertex	NNI site 2/thumb 2
ABT-072	AbbVie	NNI site 3/palm 1
HCV-796	ViroPharma/Wyeth	NNI site 4/palm 2
Filibuvir (PF-00868554)	Pfizer	NNI site 2/thumb 2
IDX375	Idenix	NNI site 4/palm 2
Tegobuvir (GS-9190)	Gilead	NNI site 4/palm 2
GS-9669	Gilead	NNI site 3/palm 1
Deleobuvir	Böhringer	NNI site 3/palm 1
Host targeting agents
NIM811	Novartis	Cyclophilin inhibitor
Alisporivir (Debio-025)	Novartis	Cyclophilin inhibitor

Citation: Morozov VA, Lagaye S. Hepatitis C virus: Morphogenesis, infection and therapy. World J Hepatol 2018; 10(2): 186-212
URL: https://www.wjgnet.com/1948-5182/full/v10/i2/186.htm
DOI: https://dx.doi.org/10.4254/wjh.v10.i2.186