HEPATITIS C VIRUS: AN OUTLINED REVIEWHTML Full Text
HEPATITIS C VIRUS: AN OUTLINED REVIEW
S. D. Labhade *, Y. B. Zambare 1, S. S. Chitlange 1, R. B. Saudagar 2, Swamy Mahadevan 1 and Saras Tiwari 1
Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research 1, Pimpri, Pune - 411018, Maharashtra, India.
R. G. Sapkal College of Pharmacy 2, Nashik - 422213, Maharashtra, India.
ABSTRACT: Chronic hepatitis C (CHC) is a big cause of liver-related fibrosis and cirrhosis. The level of fibrosis is usually in the past (established by histology). The prognosis is estimated using fibrosis progression rates (FPRs; the annual probability of progressing across histological stages). However, new non-invasive options are quickly replacing biopsy. As the rates of HCV cirrhosis go on increasing and hence remains high, the morbidity and mortality of HCV- related HCC. Reduced complications from cirrhosis, including HCC, is one of the long term goals of antiviral. The new directly acting antiviral development with high rates of virological clearance has restructured the cure of HCV infection. Fewer patients remain at risk for hepatocellular carcinoma, especially those with the severe fibrosis and cirrhosis in spite of the development of HCC in HCV patients who achieve disease sustained virologic response is reduced. This review puts lights upon the overview, morphogenesis, infection, therapies. The discussion outlined will be helpful to the chemist and learners of the exact mechanism and set the broad spectrum identification of creative anti-HCV compounds. The prime objective of the review is to provide insights on HCV medicinal chemistry. In spite of promising significant advances, noteworthy difficulties stay for reducing HCV-related morbidity and mortality.
Antiviral agents, Hepatitis, Hepatocytoprotective, Fibrosis
INTRODUCTION: Hepatitis is one of the most serious diseases in the world. The biggest organ in the human body is the liver affected by this disease. It has an area in the upper right of midriff and about the size of a football. We can't live without the working of the liver. It is the warehouse and body’s filter. It can have a serious impact on human working when something turns out badly as practically all tissues and cells rely upon the liver.
The level of certain substances in the body is regulated by the liver like fats, hormones, and carbohydrates, which are essential for survival and are potentially harmful when out of balance. An essential role of the liver is digesting food since it processes the formation of bile. The blood-clotting factor is controlled by the liver, which counteracts uncontrolled bleeding. Inflammation (swelling) of the liver is eluded as hepatitis.
The ancient greek word hepa alludes to the liver, and it implies swelling (as in joint pain, dermatitis, and pancreatitis) 1. Exposure to poisons and chemicals, for example, an excessive amount of liquor, an abnormal immune response to healthy assault tissues in the body, fat which may lead to build-up of fat in liver disease, microbes, including viruses, is a significant reason for hepatitis. A hepatocyte is the main tissue of the liver. Hepatocytes make up 70-85% of the liver's cytoplasmic mass. It gives the best conditions to these viruses like HAV, HBV, and HCV to replicate. As a reaction to this infection, the body's immune system targets the liver, which causes Swelling (hepatitis). On the off chance that where the inflammation is extreme (which can occur with HAV and HBV) or continues for a significant time period (which can occur with HBV and HCV), large amount of scar tissue in the liver, a condition is called as fibrosis. It occurs when the liver attempts to repair and replace damaged cells.
The normal flow of blood throughout the liver is blocked by formed hardened scared tissue instead of normal liver tissue and truly influences its structure and capacity to function legitimately after the long time infection because of this virus. This procedure is called cirrhosis. Blood gets accumulated into the spleen and the digestive organs if the liver is seriously harmed, causing increased tension in these organs 2. This condition is called portal hypertension includes loss of blood and ascites (build-up of fluid in the abdomen). Significant liver harm diminishes the formation of bile required for correct digestion, and it can diminish the liver's capacity to store and process supplements required for survival. Liver damage affects the ability to remove toxins from the bloodstream, which can eventually lead to mental confusion and even coma (hepatic encephalopathy). There are five viruses that affect the liver and give rise to hepatitis: Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, the delta hepatitis infection (HDV, which only causes problems for people infected with HBV) and hepatitis E infection (Hepatitis E virus). Most of the death occurs due to cirrhosis or liver cancer in men and women acquired with HBV and HCV infection 3, 4.
Although on average, globally, 84% of vaccines exist, vaccines are not always protective for infants whose mother has high viral loads. Even though several drug treatments are available as antiviral drugs for hepatitis B and C, but it is not available in a developing countries and not even cost-effective. To date, there is no vaccine reported for HCV as the genotype of virus observed in different areas is different. HCV virus exists at least in 6 distinct genetic forms (genotypes) with multiple subtypes. Almost 50 subtypes have been identified. A global vaccine to be developed so as to protect against all these variants of the virus. Even if several anti-viral drugs, including HuIFN-alpha-Le and nucleoside analog reverse transcriptase inhibitors, have been used for the hepatitis B treatment. Still, huge issues remain as including moderate efficacy, dose-related adverse effects, and drug effective due to resistance. Along these lines, the remarkable medical requirement for safe and effective anti- HCV drugs exists, and finding new anti-HCV agents remains a challenge 5, 6.
HCV is a tiny engulfed virus that has a single-stranded RNA genome, positive-sense that encodes a large polyprotein of 3010 amino acids. In order to form mature structural and non-structural (NS) proteins, the polyprotein is co- and post-translationally processed by cellular and virally encoded proteases. For viral maturation and replication, the NS3 serine-like protease enzyme and RNA- dependent RNA polymerase (RdRp) is essential 7-10.
Symptoms: Infection for longer period of time with the hepatitis C virus (HCV) is known as chronic hepatitis C. Signs, and symptoms of these infections are abnormal bleeding, contusion, Fatigue, loss of appetite, yellow pigmentation of the skin and eyes (jaundice), Dark urine, Itchy skin 11-13. Fluid development in your stomach area, retention of fluid in leg tissues causing edema, reduced weight, disconcertion, sleep disorder and dysarthria, spider naevus.
Structure: HCV is an enveloped, positive-stranded RNA virus classified in hepavirus genus within Flaviviridae family. It has 7 genotypes, and HCV 84 subtypes currently recognized 14-18.
Life Cycle: HCV life cycle is tightly linked to the lipid metabolism of the hepatocyte. HCV utilizes the liver cell for its development. The virus is located with the protein-specific layer.
Locate and connect these proteins to an element called a receptor on the surface of liver cells. The receptor gets signals for liver cells. The virus reaches the external barrier of liver cells. Then, the barrier surrounds the virus picks it up and put it in the cell.
The coating of virus breaks down viral RNA carrier genetic information is propagated into a liver cells. Viral RNA is ready for reproduction. It imitates the RNA of liver cells and starts to make its RNA products. It can also inhibit the proper functioning of liver cells. Sometimes, the viral RNA also triggers the reproduction of liver. Things amplify as viral RNA builds a template to replicate itself. The virus replication mechanism is not fully grasped. Time and again,, viral RNA is cloned to produce fresh viruses. The coating of viruses consists of various protein-based coverings. These are created and released during this phase by ribosomes or cell proteins builders 19-21.
Capsomers (proteins units) come together and form new particles around the viral RNA. These create sphere-shaped coverings, called as a capsid. The virus's genetic material is protected by it. In the end stage, the virus produces a bud inside in the final phase. The bud is surrounded by a protective cover. It is propagated through the liver cell barrier, ready to infect another cell in the liver. This procedure goes on till the infected liver cells die. 9600 bases are there in the HCV genome, which is edged by 5’ and 3’ non-translated region as a continuous open reading frame. Internal ribosome entry site is essential to initiate the translation of the HCV genome at 5’ non-translated region.
Approximately 3000 = 3300 amino acid polyprotein precursor is produced by the IRES-mediated translation process, which cleaves co subsequently and post-translationally into mature viral structural and non- structural proteins. Enzyme cellular peptidases and two viral proteases NS2/3 and NS3 cause proteolytic processing of polyproteins, which leads to break into 10 functional subunits like C, E1, E2, P7, NS2, NS3, NS4A, NS4B, NS5A, NS5B. Where C, E1, E2 subunits from virus particles in which nucleocapsid is nonstructural from repeated copies of core proteins (C) and E1, E2 form (glycoprotein) envelope. Assembly and release of virus particles is a function of P7. Virus replicate complex formed from NS Proteins 23-26. Below is the figure of the HCV virus and its life cycle.
FIG. 1: DIAGRAM OF HCV VIRUS
FIG. 2: HCV LIFE CYCLE; 1) BINDING & ENTRY 2) FUSION AND UNCOATING OF CAPSID 3) TRANSLATION 4) REPLICATION ON MEMBRANE BOUND 5) ASSEMBLY 6) TRANSPORT, MATURATION AND RELEASE
HCV Transmission Routes: Main route of HCV infection is blood and blood products. Transfusion of clotting factors, blood transfusion of unscreened products, organ transplantation, medical instrument reuse (like syringes, cathartics, needles, infusion sets), etc. may be the cause of HCV infection. Unsafe sex is but controversial.
Mother to child transmission, human immunodeficiency virus, co-infected mothers during normal delivery, C section are the HCV transmission modes. It is also seen that the use of tattoos, sharing razors, and acupuncture may cause infection. Casual household contact and contact with the saliva of those infected are inefficient modes of transmission 27-30.
Mode of Transmission: The essential mode of HCV transmission is a blood-borne transmission. Hazardous infusion hones in healthcare settings and recreational infusion medicate utilization are especially vital for HCV transmission around the world 31. In joined together, states in 1992 earlier to the screening of blood items for HCV starting, the healthcare-associated transmission of HCV happened more habitually; in any case, 33 healthcare episodes including more than 239 outbreak-associated cases were detailed to the Centers for Illness Control and Avoidance [CDC] from 2008–2015 72.
Vertical transmission can happen in ~6% of newborn children born to HCV-infected moms and transmission may be twice as likely to happen in newborn children born to HCV/HIV co-infected moms or HCV mono-infected moms with tall viral loads 32-36.
Sexual transmission is for the most part wasteful; in any case, an expanding number of cases of sexually transmitted disease have been detailed among HIV-infected men who have sex with men [MSM]. At last, HCV transmission has too been detailed within the setting of non-injection sedate use as well as within the setting of unregulated tattoos 37.
Testing and Diagnosis: Research facility determination of persistent HCV contamination within the Joined together States as of now requires the utilize of two sorts of tests: immunoglobulin (Ig) G antibody chemical immunoassays (anti-HCV) and nucleic acid tests (NAT). HCV testing ought to be started with an anti-HCV counteracting agent test 38. People without hazard variables for HCV and a non-reactive anti-HCV counteracting agent require no advance assessment for HCV contamination. Additional testing may be suitable for certain populaces with seriously compromised resistant frameworks or current dangers for HCV introduction such as infusion sedate utilize or hemo dialysis 39. A responsive anti-HCV counteracting agent requires affirmation with an HCV NAT to decide the nearness of HCV RNA and current HCV contamination. People with a reactive anti-HCV antibody and a positive HCV NAT are infected with HCV and ought to be connected to suitable HCV therapeutic care and treatment 40. Diagnostic: For HCV diagnosis, both serologic and nucleic acid-based tests were developed 41-48.
Serologic tests are adequate when constant hepatitis C is anticipated, with a sensitivity of more than 99% in case utilizing the 3rd generation assays. Positive serologic comes about require extra HCV RNA or (with somewhat decreased sensitivity) HCV center antigen estimations in arrange to distinguish between chronic hepatitis C and settled HCV disease from the past. When an acute hepatitis C is considered, a serologic screening alone is inadequate, since mature anti-HCV antibodies are developed late after transmission of the infection 49-51. Because of low sensitivity, poor specificity, and low efficacy compared to serologic and nucleic acid-based approaches, morphological methods like immune histo-chemistry, in situ hybridization, or PCR from liver specimens does not play any relevant role. HCV core antigen assay: There are 5 different antibodies targeted the HCV core in the assay 52-56.
Diagnosis: Serologic Assays that detect human antibodies generated as a response to HCV infection is done in initial testing for the diagnosis of HCV infection. Laboratory diagnosis for the HCV infection test requires the use of 2 types of test- (IgG) antibody enzyme immunoassays nucleic acid test (NA) 57-65. Diagnosis is recommended in those patients who have a high level of ALT. Amplification techniques such as polymerase chase reaction may be used to detect HCV RNA in blood. Depending upon the severity of the infection and its diagnosis, therapeutic decision making, assessment of virological response to therapy can be done.
The cost of new HCV core antigen assay method is low, in spite of the fact that, to some degree, less sensitive, elective for nucleic acid testing for HCV 66-67. The early diagnosis of acute hepatitis C should be done and considered as mandatory as it is detectable in a few days of infection. The nucleic acid-based tests are available and are efficient 68.
The HCV RNA measurement is besides vital in determination of the HCV genotype, selection of treatment procedure, therapy duration, and assessment of the treatment success HCV RNA estimation. For a number of antiviral combination treatments, the HCV RNA follow-up thinks about are fundamental to characterize the result of the treatment and encourage helpful techniques, if vital 69.
Traditionally, in order to evaluate that a sustained virologic response (SVR) was achieved or not, the tests should be repeated until 24 wk after treatment completion. However, Now the 12 wk is the new time point for evaluation of the final outcome of virological treatment, and after the end-of-treatment, the interference of a virologic decadence is equal after 12 and 24 wk 70-75 and for the both qualitative as well as quantitative, PCR-based detection assays method are available. The initial diagnostic of hepatitis C is done using qualitative PCR tests being sensitive, and for a screening of blood, organ donations and for confirming SVR after treatment completion, qualitative PCR assays are used 76-78. Quantitative reverse transcriptase (RT) real-time PCR-based assays can detect and quantify the HCV RNA over a very wide range, from approximately 10 IU/ml to 10 million IU/ml. In the treatment monitoring, when the virus load is gradually reducing, the measurements are essential 76, 77. Identification of HCV genotyping is also a very important factor for the patients who are recommended for antiviral therapy. And for assessment of the HCV genotyping, both direct sequence analysis and reverse hybridization technology are used. The only drawback is that these methods do not assess the genome subtypes, and because of this drawback, currently assays were additionally analyzing the coding regions. Genes encoding core protein and the NS5B gives non-overlapping sequence differences between the genotypes and subtypes 78.
Treatment: Chronic HCV infected patient needs to be treated as early as possible.
i) If cirrhosis and fibrosis bridging is there in patients needs to be treated at earliest so as to avoid the propagation of cirrhosis.
ii) Liver transplant recipients should be treated.
iii) If any extrahepatic manifestations are there in patient need to be treated 79, e.g., Porphyria cutaneatarda or glomerulonephritis- treatment is recommended.
In order to avoid the risk of transmission of disease during the delivery of the infant, women should be treated before being pregnant 80. Treatment during pregnancy is not recommended. There are several antiviral drugs that can be used for the treatment of HCV infection. There have been made significant advances in treatment for HCV using new direct-acting antiviral medications, sometimes in combination with the existing ones 88-90. HCV genotype, Severity of liver damage, other medical conditions, and prior treatment decide the choice of medications, length of treatments. WHO recommends treatment to all individuals diagnosed with HCV infection who are 12 years of age or older, irrespective of disease stage. Who recommends treatment to adolescents aged of 12-17 years, weighing 36 kg at least with HCV infection 81-83. Now a day’s medication prescribed is as given in Table 2.
TABLE 1: AS PER WHO TREATMENT REGIMENS FOR HCV INFECTION
|S. no.||Drugs treatment||Duration||Genotype|
|1||Sofosbuvir/ledipasvir||12 weeks||G1, 4,5,6|
|2||Sofosbuvir/ribavirin||12 weeks||Genotype 2|
|3||Sofosbuvir/ribavirin||24 weeks||Genotype 3|
A treatment regimen differs until 12 years of age. Treatment with interferon-based regimens should no longer be used
TABLE 2: DAY TO DAY MEDICATION PRESCRIBED
|S. no.||Drug treatment||Duration|
|1||Daclastasvir (Datelinza) with Sofobuvir||12 weeks|
|2||Sofobuvir- velpatasvir (Epclersa)||12 weeks|
|3||Lalipasvir- sofobuvir (Harvoni)||8-12 weeks|
|4||Gleaprevir and pibrentasvir(Mavqret)||8 weeks (who don’t have cirrhosis and have not been treated, treatment is longer at different disease stage)|
|5||Ribavirin (Copegus, Moderika, Rebeto, Ribasphere, Virazole)||24-48 weeks or longer|
|6||Sofosbuvir (Sovaldi) with interferon and ribavirin||12 to 24 weeks|
|7||Ombitasvir-paritaprevir- ritonavir (Technivie) along with ribavirin|
|8||Ombitasvir- paritaprevir-dasabuvir-ritonavir(Viekira pack)||12-24 weeks|
|9||Sofobuvir- velpatasvir-voxilaprovir (Vosavi) –Chronic HCV infection||12-24 weeks|
|10||Elbasvir-grazoprevir(Zepatier)||Once daily 12 -24 weeks|
According to some randomized trial combination of interferon and Glycyrrhizin is more effective than single interferon therapy, which used in the treatment of chronic hepatitis c, and the patient in which single used interferon are ineffective 83.
CONCLUSION: HCV is infectious. The most common reason is unsafe injections, transmitted by percutaneous blood exposure. It seems to be endemic in most parts of the world. Long term complication of HCV infection includes cirrhosis and hepatocellular carcinoma. Fundamental studies on virus-cell interactions and studies directing towards the development of the prophylactic vaccine should be intensified. There are several advances in HCV treatment have created new opportunities for reducing HCV-associated morbidity and mortality. These treatments are safe, well-tolerated, and highly effective. However, the benefits cannot be realized without a significant increase in the number of persons tested for HCV so that all chronically infected individuals can be aware of their diagnosis and linked to appropriate clinical care.
ACKNOWLEDGEMENT: The author thanks DYPIPSR for providing the necessary facility to complete work.
CONFLICTS OF INTEREST: The author(s) confirms that there is no conflict of interest.
- Ly KN, Hughes EM, Jiles RB and Holmberg SD: Rising mortality associated with hepatitis C virus in the United States, 2003-2013. Cli Infect Dis 2016; 62(10): 1287-8.
- Allison RD, Tong X, Moorman AC, Ly KN, Rupp L, Xu F, Gordon SC and Holmberg SD: Chronic Hepatitis Cohort Study (CHeCS) Investigators. Increased incidence of cancer and cancer-related mortality among persons with chronic hepatitis C infection 2006-2010. Journal of Hepatology 2015; 63(4): 822-8.
- AASLDI: HCV Guidance: Recommendations for Testing. Managing and Treating Hepatitis C 2016.
- Smith BD, Morgan RL, Beckett GA, Falck-Ytter Y, Holtzman D, Teo CG, Jewett A, Baack B, Rein DB, Patel N and Alter M: Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. Morbidity and Mortality Weekly Report: Recommendations and Reports 2012; 61(4): 1-32.
- Alter MJ and Margolis HS: Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease.
- World Health Organization. http://www. who. int/ mediacentre/factsheets/fs340/en.
- De Francesco R, Tomei L, Altamura S, Summa V, Migliaccio G. Approaching a new era for hepatitis C virus therapy: inhibitors of the NS3-4A serine protease and the NS5B RNA-dependent RNA polymerase. Antiviral Research 2003; 58(1): 1-6.
- Beaulieu PL and Tsantrizos YS: Inhibitors of the HCV NS5B polymerase: new hope for the treatment of hepatitis C infections. Current Opinion in Investigational Drugs (London, England: 2000) 2004; 5(8): 838-50.
- Lindenbach BD, Evans MJ, Syder AJ, Wölk B, Tellinghuisen TL, Liu CC, Maruyama T, Hynes RO, Burton DR, McKeating JA and Rice CM: Complete replication of hepatitis C virus in cell culture. Science 2005; 309(5734): 623-6.
- Fraser CS and Doudna JA: Structural and mechanistic insights into hepatitis C viral translation initiation. Nature Reviews Microbiology 2007; 5(1): 29.
- Fukushi S, Katayama K, Kurihara C, Ishiyama N, Hoshino FB, Ando T and Oya A: Complete 5′ noncoding region is necessary for the efficient internal initiation of hepatitis C virus RNA. Biochemical and biophysical research communications 1994; 199(2): 425-32.
- Targett-Adams P, Hope G, Boulant S and McLauchlan J: Maturation of hepatitis C virus core protein by signal peptide peptidase is required for virus production. Journal of Biological Chemistry 2008; 283(24): 16850-9.
- Ashfaq UA, Javed T, Rehman S, Nawaz Z and Riazuddin S: An overview of HCV molecular biology, replication and immune responses. Virology Journal 2011; 8(1): 161.
- Mohd Hanafiah K, Groeger J, Flaxman AD and Wiersma ST: Global epidemiology of hepatitis C virus infection: new estimates of age‐specific antibody to HCV seroprevalence. Hepatology 2013; 57(4): 1333-42.
- Roingeard P and Hourioux C: Hepatitis C virus core protein, lipid droplets and steatosis. Journal of viral hepatitis 2008; 15(3): 157-64.
- Roingeard P and Depla M: The birth and life of lipid droplets: learning from the hepatitis C virus. Biol Cell 2011; 103: 223-31.
- Williamson CD and Colberg‐Poley AM: Access of viral proteins to mitochondria via mitochondria‐associated membranes. Reviews in Med Virol 2009; 19(3): 147-64.
- Dubuisson J and Cosset FL: Virology and cell biology of the hepatitis C virus life cycle–an update. Journal of Hepatology 2014; 61(1): S3-13.
- Deleersnyder V, Pillez A, Wychowski C, Blight K, Xu J, Hahn YS, Rice CM and Dubuisson J: Formation of native hepatitis C virus glycoprotein complexes. Journal of Virology 1997; 71(1): 697-04.
- Weiner AJ, Christopherson C, Hall JE, Bonino F, Saracco G, Brunetto MR, Crawford K, Marion CD, Crawford KA, Venkatakrishna S and Miyamura T: Sequence variation in hepatitis C viral isolates. J of Hepatology 1991; 13: S6-14.
- Cocquerel L, Meunier JC, Pillez A, Wychowski C and Dubuisson J: A retention signal necessary and sufficient for endoplasmic reticulum localization maps to the trans-membrane domain of hepatitis C virus glycoprotein E2. Journal of Virology 1998; 72(3): 2183-91.
- Farci P, Bukh J and Purcell RH: The quasispecies of hepatitis C virus and the host immune response. In Springer seminars in immunopathology 1997; 19(1): 5-26.
- Penin F, Brass V, Appel N, Ramboarina S, Montserret R, Ficheux D, Blum HE, Bartenschlager R and Moradpour D: Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A. Journal of Biological Chemistry 2004; 279(39): 40835-43.
- Flint M and McKeating JA: The role of the hepatitis C virus glycoproteins in infection. Reviews in Medical Virology 2000; 10(2): 101-17.
- Barth H, Cerino R, Arcuri M, Hoffmann M, Schürmann P, Adah MI, Gissler B, Zhao X, Ghisetti V, Lavezzo B and Blum HE: Scavenger receptor class B type I and hepatitis C virus infection of primary tupaia hepatocytes. Journal of Virology 2005; 79(9): 5774-85.
- Carrère-Kremer S, Montpellier-Pala C, Cocquerel L, Wychowski C, Penin F and Dubuisson J: Subcellular localization and topology of the p7 polypeptide of hepatitis C virus. Journal of virology 2002; 76(8): 3720-30.
- Sakai A, Claire MS, Faulk K, Govindarajan S, Emerson SU, Purcell RH and Bukh J: The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences. Proceedings of the National Academy of Sciences 2003; 100(20): 11646-51.
- Fan X, Xue B, Dolan PT, LaCount DJ, Kurgan L and Uversky VN: The intrinsic disorder status of the human hepatitis C virus proteome. Molecular Bio Systems 2014; 10(6): 1345-63.
- Grakoui A, McCourt DW, Wychowski C, Feinstone SM and Rice CM: Characterization of the hepatitis C virus-encoded serine proteinase: determination of proteinase-dependent polyprotein cleavage sites. J of Virol 1993; 67(5): 2832-43.
- Dumoulin FL, von dem Bussche A, Li J, Khamzina L, Wands JR, Sauerbruch T and Spengler U: Hepatitis C virus NS2 protein inhibits gene expression from different cellular and viral promoters in hepatic and nonhepatic cell lines. Virology 2003; 305(2): 260-6.
- Erdtmann L, Franck N and Lerat H: The hepatitis C virus NS2 protein is an inhibitor of CIDE-B-induced apoptosis. J Biol Chem 2003; 278: 18256-64.
- Pawlotsky JM: Treating hepatitis C in “difficult-to-treat” patients. New England J of Medi 2004; 351(5): 422-3.
- Frese M, Pietschmann T, Moradpour D, Haller O and Bartenschlager R: Interferon-α inhibits hepatitis C virus subgenomic RNA replication by an MxA-independent pathway. J of General Virology 2001; 82(4): 723-33.
- Lin C, Thomson JA and Rice CM: A central region in the hepatitis C virus NS4A protein allows formation of an active NS3-NS4A serine proteinase complex in-vivo and in-vitro. Journal of Virology 1995; 69(7): 4373-80.
- Foy E, Li K, Wang C, Sumpter R, Ikeda M, Lemon SM and Gale M: Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science 2003; 300(5622): 1145-8.
- Li X, Jeffers LJ, Shao L, Reddy KR, De Medina M, Scheffel J, Moore B and Schiff ER: Identification of hepatitis C virus by immunoelectron microscopy. Journal of Viral Hepatitis 1995; 2(5): 227-34.
- Sumpter R, Loo YM, Foy E, Li K, Yoneyama M, Fujita T, Lemon SM and Gale M: Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I. Journal of Virology 2005; 79(5): 2689-99.
- Sakamuro D, Furukawa T and Takegami T: Hepatitis C virus nonstructural protein NS3 transforms NIH 3T3 cells. Journal of Virology 1995; 69(6): 3893-6.
- Fujita T, Ishido S, Muramatsu S, Itoh M and Hotta H: Suppression of actinomycin D-induced apoptosis by the NS3 protein of hepatitis C virus. Biochemical and Bio-physical Research Communications 1996; 229(3): 825-31.
- Borowski P, Heiland M, Oehlmann K, Becker B, Kornetzky L, Feucht H and Laufs R: Non‐Structural Protein 3 of Hepatitis C Virus Inhibits Phosphorylation Mediated by cAMP‐Dependent Protein Kinase. European Journal of Biochemistry 1996; 237(3):611-8.
- Hassan M, Ghozlan H and Abdel-Kader O: Activation of c-Jun NH2-terminal kinase (JNK) signaling pathway is essential for the stimulation of hepatitis C virus (HCV) non-structural protein 3 (NS3)-mediated cell growth. Virology 2005; 333(2): 324-36.
- Kim JL, Morgenstern KA, Griffith JP, Dwyer MD, Thomson JA, Murcko MA, Lin C and Caron PR: Hepatitis C virus NS3 RNA helicase domain with a bound oligo-nucleotide: the crystal structure provides insights into the mode of unwinding. Structure 1998; 6(1): 89-100.
- Cho HS, Ha NC, Kang LW, Chung KM, Back SH, Jang SK and Oh BH: Crystal structure of RNA helicase from genotype 1b hepatitis C virus a feasible mechanism of unwinding duplex RNA. Journal of Biological Chemistry 1998; 273(24): 15045-52.
- You S, Stump DD, Branch AD and Rice CM: A cis-acting replication element in the sequence encoding the NS5B RNA-dependent RNA polymerase is required for hepatitis C virus RNA replication. J of Viroy 2004; 78(3): 1352-66.
- Gwack Y, Kim DW, Han JH and Choe J: DNA helicase activity of the hepatitis C virus nonstructural protein 3. European Journal of Biochemistry 1997; 250(1): 47-54.
- Tai CL, Chi WK, Chen DS and Hwang LH: The helicase activity associated with hepatitis C virus nonstructural protein 3 (NS3). J of Virology 1996; 70(12): 8477-84.
- Levin MK, Gurjar M and Patel SS: A Brownian motor mechanism of translocation and strand separation by hepatitis C virus helicase. Nature Structural & Molecular Biology 2005; 12(5): 429.
- Zhang C, Cai Z, Kim YC, Kumar R, Yuan F, Shi PY, Kao C and Luo G: Stimulation of hepatitis C virus (HCV) nonstructural protein 3 (NS3) helicase activity by the NS3 protease domain and by HCV RNA-dependent RNA polymerase. Journal of Virology 2005; 79(14): 8687-97.
- Hügle T, Fehrmann F, Bieck E, Kohara M, Kräusslich HG, Rice CM, Blum HE and Moradpour D: The hepatitis C virus nonstructural protein 4B is an integral endoplasmic reticulum membrane protein. Viro 2001; 284(1): 70-81.
- Lundin M, Monné M, Widell A, Von Heijne G and Persson MA: Topology of the membrane-associated heap-titis C virus protein NS4B. J of Vir 2003; 77(9): 5428-38.
- Elazar M, Cheong KH, Liu P, Greenberg HB, Rice CM and Glenn JS: Amphipathic helix-dependent localization of NS5A mediates hepatitis C virus RNA replication. Journal of Virology 2003; 77(10): 6055-61.
- Penin F, Brass V, Appel N, Ramboarina S, Montserret R, Ficheux D, Blum HE, Bartenschlager R and Moradpour D: Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A. Journal of Biological Chemistry 2004; 279(39): 40835-43.
- Tellinghuisen TL, Marcotrigiano J, Gorbalenya AE and Rice CM: The NS5A protein of hepatitis C virus is a zinc metalloprotein. J of Bio Chem 2004; 279(47): 48576-87.
- Elazar M, Cheong KH, Liu P, Greenberg HB, Rice CM and Glenn JS: Amphipathic helix-dependent localization of NS5A mediates hepatitis C virus RNA replication. J Virol 2003; 77: 6055-61.
- Penin F, Dubuisson J, Rey FA, Moradpour D and Pawlotsky JM: Structural biology of hepatitis C virus. Hepatology 2004; 39(1): 5-19.
- Shi ST, Lee KJ, Aizaki H, Hwang SB and Lai MM: Hepatitis C virus RNA replication occurs on a detergent-resistant membrane that cofractionates with caveolin-2. Journal of Virology 2003; 77(7): 4160-8.
- Tu H, Gao L, Shi ST, Taylor DR, Yang T, Mircheff AK, Wen Y, Gorbalenya AE, Hwang SB and Lai MM: Hepatitis C virus RNA polymerase and NS5A complex with a SNARE-like protein. Virology 1999; 263(1): 30-41.
- Gao L, Aizaki H, He JW and Lai MM: Interactions between viral nonstructural proteins and host protein hVAP-33 mediate the formation of hepatitis C virus RNA replication complex on lipid raft. Journal of Virology 2004; 78(7): 3480-8.
- Appel N. Pietschmann T. Bartenschlager R.: Mutational analysis of hepatitis C virus nonstructural protein 5A: potential role of differential phosphorylation in RNA replication and identification of a genetically flexible domain. J Virol 2005; 79: 3187-94.
- Shimakami T, Hijikata M, Luo H, Ma YY, Kaneko S, Shimotohno K and Murakami S: Effect of interaction between hepatitis C virus NS5A and NS5B on hepatitis C virus RNA replication with the hepatitis C virus replicon. Journal of Virology 2004; 78(6): 2738-48.
- Wang C, Gale Jr M, Keller BC, Huang H, Brown MS, Goldstein JL and Ye J: Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mole Cell 2005; 18(4): 425-34.
- Ye J, Wang C, Sumpter R, Brown MS, Goldstein JL and Gale M: Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proceedings of the National Academy of Sciences 2003; 100(26): 15865-70.
- Tan SL and Katze MG: How hepatitis C virus counteracts the interferon response: the jury is still out on NS5A. Virology 2001; 284(1): 1-2.
- Roussel J, Pillez A, Montpellier C, Duverlie G, Cahour A, Dubuisson J and Wychowski C: Characterization of the expression of the hepatitis C virus F protein. Journal of General Virology 2003; 84(7): 1751-9.
- Varaklioti A, Vassilaki N, Georgopoulou U and Mavromara P: Alternate translation occurs within the core coding region of the hepatitis C viral genome. Journal of Biological Chemistry 2002; 277(20): 17713-21.
- Xu Z, Choi J, Lu W and Ou JH: Hepatitis C virus f protein is a short-lived protein associated with the endoplasmic reticulum. J Virol 2003; 77: 1578-83.
- Pisani F, Fazio A, Artesi C, Russo M, Trio R, Oteri G, Perucca E and Di Perri R: Elevation of plasma phenytoin by viloxazine in epileptic patients: a clinically significant drug interaction. Journal of Neurology, Neurosurgery & Psychiatry 1992; 55(2): 126-7.
- Samrat SK, Li W, Singh S, Kumar R and Agrawal B: Alternate reading frame protein (F protein) of hepatitis C virus: paradoxical effects of activation and apoptosis on human dendritic cells lead to stimulation of T cells. PLOS One 2014; 9(1): e86567.
- Von HT and Rice CM: Hepatitis C virus entry. Journal of Biological Chemistry 2008; 283(7): 3689-93.
- Getchell JP, Wroblewski KE, DeMaria Jr A, Bean CL, Parker MM, Pandori M, Dufour DR, Busch MP, Brecher ME, Meyer WA and Pesano RL: Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR. Morbidity and Mortality Weekly Report 2013; 62(18): 362.
- Scott JD and Gretch DR: Molecular diagnostics of hepatitis C virus infection: a systematic review. Jama 2007; 297(7): 724-32.
- Mederacke I, Wedemeyer H, Ciesek S, Steinmann E, Raupach R, Wursthorn K, Manns MP and Tillmann HL: Performance and clinical utility of a novel fully automated quantitative HCV-core antigen assay. Journal of Clinical Virology 2009; 46(3): 210-5.
- Medici MC, Furlini G, Rodella A, Fuertes A, Monachetti A, Calderaro A, Galli S, Terlenghi L, Olivares M, Bagnarelli P and Costantini A: Hepatitis C virus core antigen: analytical performances, correlation with viremia and potential applications of a quantitative, automated immunoassay. Journal of Cli Virology 2011; 51(4): 264-9.
- Vermehren J, Susser S, Berger A, Perner D, Peiffer KH, Allwinn R, Zeuzem S and Sarrazin C: Clinical utility of the Architect HCV Ag assay for early treatment monitoring in patients with chronic hepatitis C genotype 1 infection. Journal of Clinical Virology 2012; 55(1): 17-22.
- Sarrazin C, Berg T, Ross RS, Schirmacher P, Wedemeyer H, Neumann U, Schmidt HH, Spengler U, Wirth S, Kessler HH and Peck-Radosavljevic M: Prophylaxis, diagnosis and therapy of hepatitis C virus (HCV) infection: the German guidelines on the management of HCV infection. Zeitschrift fur Gastro 2010; 48(2): 289.
- Yoshida EM, Sulkowski MS, Gane EJ, Herring RW, Ratziu V, Ding X, Wang J, Chuang SM, Ma J, McNally J and Stamm LM: Concordance of sustained virological response 4, 12 and 24 weeks post‐treatment with sofosbuvir‐containing regimens for hepatitis C virus. Hepatology 2015; 61(1): 41-5.
- Lange CM, Jacobson IM, Rice CM and Zeuzem S: Emerging therapies for the treatment of hepatitis C. EMBO Molecular Medicine 2014; 6(1): 4-15.
- Bowden DS and Berzsenyi MD: Chronic hepatitis C virus infection: genotyping and its clinical role.
- Pinho JR and de Mello MF: Hepatitis Virus scientific background: epidemiology and mechanism of carcinogenesis of hepatitis C virus (HCV). In Tropical Hemato-Oncology 2015; 117-25.
- Group WA: The alcohol, smoking and substance involvement screening test (ASSIST): development, reliability and feasibility. Addiction 2002; 97(9): 1183-94.
How to cite this article:
Labhade SD, Zambare YB, Chitlange SS, Saudagar RB, Mahadevan S and Tiwari S: Hepatitis C virus: an outlined review. Int J Pharm Sci & Res 2020; 11(8): 3556-63. doi: 10.13040/IJPSR.0975-8232.11(8).3556-63.
All © 2013 are reserved by the International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
S. D. Labhade *, Y. B. Zambare, S. S. Chitlange, R. B. Saudagar, S. Mahadevan and S. Tiwari
Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra, India.
12 November 2019
17 February 2020
10 March 2020
01 August 2020