Hepatitis+C+Sp14


 * DISEASE/DRUG OF INTEREST **:

Hepatitis C

Hepatitis is an infectious disease caused by a virus that causes inflammation of the liver. These viruses can come in three forms: Hepatitis A, B, or C. These viruses vary in their degree of severity to the infected person and form of transmission [1]. Hepatitis A being of the least severe, and Hepatitis C being the virus that can cause the most damage since: it is the most likely to become chronic and it cannot be prevented by vaccination [1]. Additionally, Hepatitis C is only transferred through blood, while Hepatitis A can be transferred through bodily fluids, and hepatitis B can be spread in either form [1]. The Hepatitis researched in the paper will be Hepatitis C.   Hepatitis C can either be diagnosed as acute or it can progress and become chronic. Acute hepatitis C is short-term and lasts about six months. When the hepatitis is acute it is usually because the body is able to get rid of the infection and the virus, without any additional treatments [3]. However, if the body cannot get rid of the virus it will become chronic, which is usually the case with Hepatitis C [2,3]. Infection of Hepatitis can be seen in symptoms of liver failure, which include: fatigue, joint and belly pain, itchy skin, sore muscles, darkening of urine, and yellowish eyes/skin [1,2]. These symptoms are usually seen in acute hepatitis. Unfortunately, most people don’t have the symptoms, and therefore can carry the virus for many years and progresses into a chronic infection [1,3]. If not treated, chronic Hepatitis C, can cause cirrhosis, liver cancer, and/or severe liver damage or failure [1,2,3]. Figure 1. Progress of the effects of Hepatitis C on the liver, obtained from http://doctorrajput.com/hepatitis/ Furthermore, hepatitis C can only be transferred through blood, which can be done in several ways: such as using infected needles or other equipment that comes into contact with blood [2,3]. Also, it can be obtained from the mother if she was infected [3], there is also a risk if the person got a blood transfusion or organ transplant before 1992 [2], and having sex with someone who is infected [3]. There is around 170 million individuals infected with Hepatitis C, and about 75% to 85% of infected of individuals with Hepatitis C will develop a chronic infection. Risk of obtaining Hepatitis C goes up if the person has HIV, and HIV carriers is the population who is most prone to a hepatitis infection [4]. African Americans are more prone than any other ethnic groups, making up 22% of the chronic Hepatitis C case [4]. Furthermore, Hepatitis is now the number one case of death in the U.S. [4], however there is no vaccine to prevent this growing public health threat.
 * MOTIVATION AND BACKGROUND **:

Even though there is no vaccine to prevent Hepatitis C, there is treatment if the hepatitis becomes chronic. It is typically treated for many months, with many drugs. These drugs include a form of interferon and Ribavrin, and an add-on therapy of Incivek and Victrelis, raising the chances of curing those infected with hepatitis C, from 50 to 80 percent. If Hepatitis C becomes resistant to the add-on drugs, however, the interferon and ribavirin lower the probabilities of this happening. This treatment targets the Hepatitis protease enzyme, which is responsible for the replication process of the virus. As shown in some research, inhibitors against Hepatitis NS3-4A protease are essential for replication of the virus, making a good place to target to cure the virus [5,6]. Proteases in a virus work in the translation process of viral RNA into a polypeptide bond, which included several individual proteins. These long chains of proteins translated are not functional when they are together. This is where the protease comes into place: the viral protease cuts the long polypeptide sequence into the individual proteins, which can then become functional. These proteins that have now become functional facilitate the replication of the Hepatitis virus. Therefore, by inhibiting the function of the protease, the production of other vital proteins is also inhibited.
 * TARGET INFORMATION **:

The most effective treatments against the Hepatitis C virus target its protease and attempt to inhibit this protein, as investigated in several articles [5,6,7]. The treatment used to inhibit the protease found in the virus is using forms of interferon, such as interferon alfa-2b. By inhibiting the normal function of the protease, the virus it will block the production other proteins necessary for virus replication. If the protease is successfully inhibited by the interferon, it will make it nearly impossible for the virus to replicate [6]. Furthermore, one research showed that the protease that blocks the phosphorylation and effector action of interferon regulatory factor-3 [7], which are important cellular antiviral signaling molecule. Therefore this research showed that by inhibiting the protease it would not only stop replication but also it would also restore other control factors of the Hepatitis infection. There are many types of interferon, and therefore they have different molecular structures. One recommended in PubMed is interferon Alfa-2b. This specific interferon is also known as K779, and has a molecular formula of C16H17Cl3I2N3NaO5S and a molecular weight of 746.545989 [8]. This interferon has had more than 400 clinical trials [8].
 * DRUG INFORMATION: **

Figure 2. Molecular structure of a type of interferon: Interferon Alfa-2b. [8]   This treatment is injected into the individual. Several types of interferon are patented, some by the FDA, and is exclusive but can given to by the doctor if necessary. Add-ons to the treatment can also be prescribed if necessary which are also patented, and given to exclusively by the doctor. Furthermore, interferon can also be used with other viruses such as HIV. However, it can also cause side effects such as depression, problems with breathing, and weight loss.

[1] Banner Health. What is the difference between Hepatitis A, B, and C? [] (accessed Feb 3, 2014) [2] WebMD. Hepatitis Health Center. [] (accessed Feb 3, 2014) [3] U.S. Department of Health and Human Services. National Digestive Diseases Information Clearinghouse (NDDIC). [|http://digestive.niddk.nih.gov/ddiseases/pubs/hepc_ez/#gets] (accesses Feb 3, 2014) [4] National Medical Association. Hepatitis C Statistics. [|http://www.nmanet.org/index.php?option=com_content&view=article&id=291&Itemid=420[accessed] Feb 3, 2014) [5] Lin, C. //Hepatitis C Viruses: Genomes and Molecular Biology;// Horizon Bioscience: Norfolk, 2006.  [6] [|Hawas UW], [|El-Halawany AM] , [|Ahmed EF] . Hepatitis C virus NS3-NS4A protease inhibitors from the endophytic Penicillium chrysogenum isolated from the red alga Liagora viscida. //PubMed .gov.// [online] Sep, 2013, p355-66. [] (accessed Feb 3, 2014)  [7] E [|ileen Foy] , [|__Kui Li__] , [|__Chunfu Wang__]__ , __[|__Rhea Sumpter Jr.__][|__Masanori Ikeda__]__ , __[|__Stanley M. Lemon__] , [|__Michael Gale Jr.__] Regulation of Interferon Regulatory Factor-3 by the Hepatitis C Virus Serine Protease. //Science.// DOI: 11.1126/science.1082604. Published Online: April 17 2003. http://www.sciencemag.org [8] PubChem. Compound. [] (accessed Feb 3, 2014).
 * REFERENCES: **