Hepatitis+C

**Motivation and Background** :
I decided to research Hepatitis C and Sovaldi because a student shared his experience with the disease at church. Because of chronic Hepatitis C infection, the young man was discriminated when he tried to find a job. He had to give up his dream job of working for one of the largest social media companies in Asia because of the stigma against this infectious disease. Just like him, more than 170 million people around the glob are currently struggling with this disease and expensive treatment options [1].

Hepatitis in general means liver inflammation. Hepatitis A, B, and C are the three types of infections caused by three different viruses. Out of the three, Hepatitis C is especially hard to prevent because of the lack of vaccine against hepatitis C virus (HCV). About 75% to 85% of people who are infected with acute Hepatitis C will acquire chronic infection. Not only is this disease difficult to prevent, it is also tricky to treat since many do not experience any symptoms after infection. Lack of early treatment can lead to long term damages to the body, including cirrhosis and liver cancer [2].

The current standard treatment consist of a protease inhibitor, pegylated interferon alfa-2a, and ribavirin. This combination needs to be taken for a long time (up to 48 weeks) and often cause either unsatisfactory results or strong side effects [3]. Research is needed to develop new drugs that are potent and affordable to the larger general public.



** Figure 1. ** Number of Incidences of Hepatitis C on the rise in non-urban and urban areas from 2006 to 2011 [4].
[1] Webster, D. P,; Klenerman, P.; Dusheiko, G. M., Hepatitis C. // The Lancet //** 2015 **, 385, 1124-35. [2] Centers for Disease Control and Prevention. Viral Hepatitis-Hepatitis C Information. [|https://www.cdc.gov/hepatitis/hcv/cfaq.htm#transmission] (accessed Feb 1, 2017). [3] Bhatia, H. K.; Singh, H.; Grewal, N.; Natt, N. K., Sofosbuvir: A novel treatment option for chronic hepatitis C infection. //Journal of Pharmacology & Pharmacotherapeutics// **2014**, 5, (4), 278-84. [4] Source: National AIDS Treatment Advocacy Project. http://www.natap.org/2014/HCV/093014_02.htm (accessed Feb 16, 2017). Copyright 2017 by NATAP. [5] Source: Astbury.leeds.ac.uk. http://www.astbury.leeds.ac.uk/Report/2000/Jager.2.htm (accessed Feb 16, 2017). Copyright 2017 by Astbury.leeds.ac.uk. [6] Protein Molecular Weight. [] (accessed Feb 2, 2017).  [7] Ranjith-Kumar, C. T.; Kao, C. C. Biochemical activities of the HCV NS5B RNA-dependent RNA polymerase. In //Hepatitis C Viruses: Genomes and Molecular Biology;// Tan S.L., Ed.; Horizon Bioscience: Norfolk, 2006; pp 293-310.  [8] Source: SciFinder. https://scifinder.cas.org/scifinder/view/scifinder/scifinderExplore.jsf (accessed Feb 2, 2017). Copyright 2017 by SciFinder.   [9] SciFinder. [] (accessed Feb 1, 2017).
 * References: **

[10]Sovaldi. Sovaldi Combination Therapy Cure Rates in Clinical Studies.http://www.sovaldi.com/about-sovaldi/study-results (accessed Feb 1, 2017). [11] Infohep. Hepatitis C Treatment Factsheet: Sofosburvir (Sovaldi). []  -treatment-factsheet-Sofosbuvir-iSovaldii/page/2845322/ (accessed Feb 1, 2017).   [12] Gilead. Highlights of Prescribing Information. [] (accessed Feb 1, 2017).

[13] DrugPatentWatch. Sovaldi Drug Profile. [] (accessed Feb 4, 2017).  [14] Mayhew, M. S., Hepatitis C treatment **2011**, 7, (10), 875-876.  [15] Mayo Clinic. Drugs and Supplements. []-supplements/ (accessed Feb 1, 2017).

**External links:**
[|https://www.cdc.gov/hepatitis/hcv/cfaq.htm#transmission] [] http://www.astbury.leeds.ac.uk/Report/2000/Jager.2.htm https://scifinder.cas.org/scifinder/view/scifinder/scifinderExplore.jsf

[|https://scifinder.cas.org/scifinder/view/scifinder/scifinderExplore.js] [] [] []

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=__**Target Information** : __=
 * Figure 2.** A ribbon diagram of the protein HCV NS5B RNA-dependent polymerase with the fingers, thumb, and palm subdomains labeled [5].

** Size ** : The molecular weight of the protein HCV NS5B RNA-dependent polymerase is 65.71 kilodaltons [6].
**Location:** NS5B works on viral RNA
 * Function in a normal cell ** : NS5B is a catalytic subunit of a replicase enzyme complex that replicates viral RNA inside HCV. It synthesizes full length RNA and can also unwind stable RNA structures [7].

=__**Drug Information**** : **__=


 * Schematic figure of drug ** :
 * Figure 3.** 2-D molecular structure of Sovaldi [8].

=

 * Delivery method ** : The drug is given orally as 400 mg/dose tablets and mainly treats chronic Hepatitis C. Sovaldi does not have to be taken with food. It is taken once or twice a day for 12 to 24 weeks depending on the genotype of the HCV [10]. Sovaldi acts as a nucleotide analogue HCV polymerase inhibitor, which attaches to the RNA in HCV to inhibit the virus from copying its genes and multiplying inside the cell [11]. More specifically, Sovaldi goes through intracellular metabolism in the liver to become active uridine analog triphosphate, which is then put into HCV RNA by the NS5B polymerase to stop genetic replication [12]. =====

** Clinical Trials Info ** : Since its production in 2014, Sovaldi has gone through 20 clinical trials [13]
__** Origin ** : __ Sofosburvir is the generic ingredient of Sovaldi. The origin of the drug is unknown [9]

** Alternatives to this drug ** : Harvoni, Boceprevir (victrelis), Telaprevir (incivek) [14]

 * Miscellaneous ** : Being cured is often referred to as having a sustained virologic response (SVR) in the medical field. SVR means that virus cannot be detected in blood 24 weeks after therapy completion [14]. Even though Sovaldi has a high cure rate of around 93%, it is important to note that response to the drug does not protect the patient from being re-infected [14, 15].