Daclatasvir Research Paper

This research paper is going to review today’s silent killer, the Hepatitis C virus. This paper will talk about the description of the disease, the signs and symptoms, the etiology and risk factors, diagnostic studies, treatments and prognosis of this disease. I had lived with this disease for over ten years before diagnosed so it is important to understand the signs and symptoms so the disease can be identified and a treatment plan can be identified as the sooner it is treated the more likely it will eradicate the disease.

HSV is a human nuclear DNA virus that can replicate in many different species of animal as well as in many different types of cells. It can gain access to different types of cells due to its 12 envelope surface glycoproteins and uses the heparan moiety of the receptors to attach to cells

Guedj, Jeremie et al. " Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life ." Proceedings of the National Academy of Sciences of the United States of America. Vol.

The immune response against HSV involves both innate and adaptive immune mechanisms. They both play pivotal role in mediating the immune responses and controlling viral pathogenesis. The first line of defence is comprised of components of innate immunity, such as various cytokines, natural killer (NK) cells and dendritic cells (DCs), which all dispense antiviral activities in eradicating the infection (Wakimoto et al., 2003). The key players of the adaptive immunity are B and T cells, which generate pathogen-specific immune response and thus control the spread of infection (Harandi et al., 2001; Kwant-Mitchell et al., 2009).

CDC 's national strategy to prevent HCV infection includes 1) prevention of transmission during high-risk activities (e.g., injection-drug use and unprotected sex with multiple partners) through risk-reduction counseling, testing, and appropriate medical management of infected persons; 2) donor screening and product inactivation procedures to eliminate transmission from blood, blood products, donor organs, and tissue; and 3) improved infection control practices to further reduce risk of transmission during medical procedures † (10).

Lamivudine(LAM) and Abacavir (ABA) are Nucleoside reverese transcriptase inhibitors which are used in the treatment of HIV . Lamivudine also used to treat the severe acute HBV hepatitis. Lamivudine is chemically known as 4 amino-1-[2R, 5S]-2-(hydroxymethyl)-1, 3-oxathiolan-5yl] pyrimidine-2-one1-3 where as Abacavir is chemically [1R-4-(2amino -6- cyclopropylamine) purine -9-yl]-1-cyclopent -2enyl] methanol 4,5. Lamivudine is practically insoluble in acetone, but very soluble in water and methanol. Abacavir17 is freely soluble in water. The drugs are available individually, as well as multicomponent dosage forms in the market. The literature review reveals that there are some analytical methods reported for Abacavir and Lamivudine either

Biostatistics allows us to monitor the fall in HCV RNA levels, which is presently used to decide whether to continue or stop pegylated interferon (IFN)-α-ribavirin combination therapy for hepatitis C patients with HCV genotype 1 infection. The monitoring of the HVC RNA determines the treatment duration, which strongly depends on the virological response during treatment, determined by measurements of on-treatment HCV RNA levels. In particular, the differentiation between ‘undetectable’ HCV RNA (target not detected) and HCV RNA ‘detectable/not quantifiable’. (4th article)

tution typically emerges when HCV genotype 1a is exposed to telaprevir.[8] Only one nucleotide change is required for the 1a subtype to develop resistance whereas two nucleotide changes must occur in genotype 1b.[10] This is not specific to PI use and has been described with other drug classes, for example, nonnucleoside polymerase inhibitors.[10] As a result, antiviral responses can vary between HCV genotype 1 subtypes during treatment with DAAs, while response was similar when treated with pegIFN and RBV dual therapy.

Genotype 1 is the most common form of HCV. Even within a single genotype there may be some slight variations. “Genotyping is important to guide treatment because some viral genotypes respond better to therapy than others. The genetic diversity of HCV is one reason that it has been difficult to develop an effective vaccine since the vaccine must protect against all genotypes.” (WHO, 2011)

HCV infection is most commonly treated with Pegylated, Interferon-a (IFN-a) and Ribavirin (18). There is a raising discussion about the IFN treatment, once is believed that it can improve neurocognitive function after clearing the virus; however, the therapy is linked to psychiatric side-effects such as depressive symptoms, fatigue and insomnia (19).

HAV targets hepatocytes which are cells of main tissue of liver. The virus is non-enveloped as it is released from the host cell via lysis of the host cell membrane without acquiring a lipid bilayer membrane from the host. Site of replication for HAV is cytoplasm of the host cell. Upon detection of hepatitis a virus cellular receptor on the target cell by viral capsid protein(s), the viral capsid undergoes conformational change releasing its genome into the host cell cytoplasm. Primary event followed by uncoating process is translation of ss (+) RNA of virus which serves as a, mRNA, translational template.

The HIV-1 diploid RNA genome is encapsulated in a lipid bilayer studded on the exterior surface with glycoproteins (reviewed by Weiss, 2013). These glycoproteins are composed a trimeric structure of three transmembrane proteins (gp41) bound to a trimeric surface glycoprotein (gp120), which together are called the envelope protein (ENV). GP120 is highly glycosylated and forms a protective glycan shield around the viral envelope. Both gp120 and gp41 can participate in binding to the CD4 epitope on the surface of T-helper cells and macrophages, thereby initiating HIV-1 infection of critical immune cells. However, progression to the point of fusing the viral lipid bilayer with the cytoplasmic membrane of CD4+ cells requires the added

The symptoms start appearing after two to five weeks of infection. The main symptoms are nausea, vomiting, diarrhea, low fever, rashes, loss of appetite and yellowing of skin (jaundice), abdominal pain. Diarrhea occurs in case of children. No specific treatment is there. Patients need adequate rest and proper nutrition. If skin becomes yellow then the patient needs a blood test or a liver panel test. If a person vomits for a long period amount of time, they get dehydrated; then, only then, hospitalization is needed. Patients should drink a plenty amount of water, or fluids. He or she should take food, which does not cause any harm to the liver. Patients should avoid tea, coffee or any alcoholic beverages, which causes harm to liver. He or she takes adequate rest. He should not take any medicine which causes harm to liver. If patient is confused about taking medicine then he or she should consult a doctor. Techniques for growing HAV in cell culture have made it possible to generate sufficient amounts of virus for vaccine production. Several inactivated or live attenuated vaccines against hepatitis A have been developed, but only four inactivated hepatitis A vaccines are currently available internationally. All four vaccines are similar in terms of efficacy and side-effect profile. The vaccines are given parenterally, as a two-dose series, 6-18 months apart. The dose of vaccine,

Hepatitis C virus (HCV) has become a major problem within the human population, affecting individuals from everywhere, but especially from poor regions. At the moment, 130 to 170 million people worldwide are infected with this virus and it keeps increasing at a rate of approximately 3.5 million people per year. (1) It is estimated that about 0.2 to 26% of the general population in different countries are chronically infected by HCV. (2)(3)

Through escape mutations the HCV virus has the ability to evade the host immune response. The infection will persist or not is determined by the strength of the immune response and the breadth of viral epitopes targeted by the T cells During acute infection. persistent infections are associated with higher escape mutants than Self-limiting HCV infections. in a variety of virus particles such as anchor proteins which allow for antigens to be presented to T cells and envelope proteins (E1 and E2) which contact the T-cell antigen receptor allowing for recognition and activation of molecules involved in antigen processing Escape mutations have been observed. Once persistence has been established, the rate of escape mutation slows and the virus often reverts to the consensus sequence for the genotype (Dustin et al., 2007). The reason for why the T cell immune response over time is changed is unknown but it is thought that the response of T cell is established early on infection with limited ability to recruit new T cells. During HCV infection, the