Antiviral agents hepatitis

Ribavirin, an antiviral agent used against hepatitis C and viral pneumonia, contains a 1,2,4-triazole ring. Why is the ring aromatic ... 

In this chapter, we have described the spectrum of antiviral activities that have been discovered beyond the world of nucleoside analogues, protease and fusion inhibitors. The compounds and mechanisms described here may one day add significantly to the armamentarium of antiviral agents, not only against Herpes Simplex, Hepatitis B and Human Immunodeficiency Virus, but also against Hepatitis C and Human Cytomegalovirus. 

Despite these intense efforts to test different chemical modifications, there is so far little success in developing potent and safe antivirals. For hepatitis C virus (HCV), McHutchison et al. reported in vivo side effects of a 20-nucleotide PS-modified ohgonucleotide (ISIS-14803) (McHutchison et al. 2006). In a test group of 28 patients, only 3 patients responded to the treatment by a reduction in the HCV viral load. The researchers concluded that further studies are needed to evaluate this novel agent and its side effects. Previously, ISIS Pharmaceuticals reported a 3.8 log reduction in plasma virus in patients with chronic HCV infection, using ISIS-14803 (www.isispharm.com). 

Interferon alfa is an antiviral agent that is effective in suppressing hepatitis B viral replication. Interferon alfa-2b and pegylated interferon alfa-2a are the only interferon therapies approved for the treatment of chronic hepatitis B. 

At month 3, if the viral count is still positive or fails to decrease at least 1 log, the patient is deemed a treatment failure. Reevaluate the patient for a different hepatitis B antiviral agent. 

Lamivudine (also known as Epivir and 3TC) is a potent antiviral drug used in the treatment of HIV and hepatitis B virus (HBV) infections. Although both enantiomers are equipotent antiviral agents, the unnatural enantiomer (with respect to natural nucleosides) is far less cytotoxic, and so a method of selectively accessing the single enantiomer was required. 

Durantel D, Alotte C, Zonlim F. (2007) Glncosidase inhibitors as antiviral agents for hepatitis B and C. Curr Opin Invest Drugs 8 125-129. 

Finally, as a specific example, the regioselective esterification of ribavirin (24) deserves to be discussed (Figure 6.6) [83]. This compound is a powerful antiviral agent used to treat hepatitis C. In order to overcome some significant side effects, it has been suggested that its administration in the form of a prodrug might improve its pharmacokinetic profile. Indeed a series of predinical evaluations showed that the alanine ester 24a possesses improved bioavailability. In... 

Another example of regioselective acylation was required for a ribavirin antiviral agent (44) used in combination with a-2-[3-interferon to treat hepatitis C (Scheme... 

Tanikawa, K. 2006. Recent advances in antiviral agents antiviral drug discovery for hepatitis viruses. Curr. Pharm. Des. 12, 1371-1377. 

Table 1 Selected macrocyclic esters and their corresponding mass spectral data. Esters were converted into hepatitis C antiviral agents after amidation with selected Intermediate Amines illustrated in Table 3...

Several compounds have been used in treating chronic viral hepatitis. Experimental and clinical studies have focused on four groups of substances (7.) antiviral agents, (2.) immunostimulants, (i.) molecular biological agents, and 4.) adjuvant medicinal remedies. The rate of spontaneous seroconversion is 8-15%lyear... 

Relapse Reactivation is often associated with the presence of wildtype HBV (80-85%) or the occurrence of precore mutants (15-20%). This event (increase of transaminases, evidence of replication markers such as HBeAg and HBV DNA, positive IgM anti-HBC, pronounced interface hepatitis) develops in 15-20% of cases 1-3 years after IFNa therapy has been stopped. In such cases the question then arises of whether to apply lamivudine. This antiviral agent is administered in cases with an unfavourable constellation or contraindication regarding IFNa, or if the patient refuses IFN. 

New antiviral agents have been based on virus-specific targets, especially the viral enzymes that are involved in the viral life cycle, i.e. responsible for the production of infectious viral particles. Research has focused on virus-encoded proteases that fulfil this role. Thus, specific inhibitors of HIV, herpesvirus and hepatitis C virus proteases are now known. Examples of clinically approved HIV pro-... 

Most of what we know about hepatitis B virus (HBV) replication has been extrapolated from studies with the two major hepadnaviral animal models the duck and the woodchuck. The unusual replication strategy of HBV was originally elucidated using the duck system, but the woodchuck model has proven to be a more useful disease system. Both animal models have been used for the evaluation of antiviral agents in in vitro and in vivo studies. 

In cultured primary duck hepatocytes (PDH) congenitally infected with duck hepatitis B virus (DHBV), all major viral replicative intermediates are generated, and CCC DNA, present initially at a low copy number, is amplified in the PDH after a few days in culture (4,5), The amplification of CCC DNA in vitro provides an alternative to liver analysis for studying the structure of this molecule and its sensitivity to potential antiviral agents. 

HAV is primarily responsible for acute hepatitis. It is most often linked to sporadic events of contaminated food in the United States and to international travel, and is usually a self-limited disease. HBV and HCV are primarily responsible for the development of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Immunomodulatory therapy and direct antiviral agents have been developed for both HBV and HCV. These therapeutic modalities require long courses of therapy and are associated with limited success. This chapter will focus on the pathophysiology, clinical course, and management of these three primary causes of viral hepatitis, namely HAV, HBV, and HCV. 

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