Antiviral drugs hepatitis virus

Viruses are small infectious agents composed of a nucleic acid genome (DNA or RNA) encased by structural proteins and in some cases a lipid envelope. They are the causative agents of a number of human infectious diseases, the most important for public health today being acquired immunodeficiency syndrome (AIDS), hepatitis, influenza, measles, and vituses causing diarrhoea (e.g., rotavirus). In addition, certain viruses contribute to the development of cancer. Antiviral drugs inhibit viral replication by specifically targeting viral enzymes or functions and are used to treat specific virus-associated diseases. 

Frick DN (2003) HeUcases as antiviral drug targets. Drug News Perspect 16 355-362 Frick DN (2006) Step-by-step progress toward understanding the hepatitis C virus RNA helicase. Hepatology 43 1392-1395... 

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. 

The resolution of racemic FTC butyrate (34) was required for the synthesis of the antiviral drug emtricitabine (Emtriva) (Scheme 7.15) a nucleoside reverse transcriptase inhibitor targeted for treatment of human immunodeficiency virus (HIV) and hepatitis infections [35]. The racemic FTC butyrate ester (34) was treated with immobilized cholesterol esterase, which cleaved the required isomer to the corresponding alcohol (-) 35 with 91% and 52% conversion [36]. The product was isolated as the hydrochloride salt to give 31% yield (98% ) from the 8 kg demonstration. The esterase was immobilized by precipitation onto an accurel polypropylene support using acetone followed by cross linking with glutaralde-... 

A number of virus diseases and virus related topics are described in this encyclopedia. Check alphabetical index for antiviral drugs, cancer research, cluckenpox, common cold coxsackie virus, dengue (breakbone fever), hepatitis, infectious mononucleosis, influenza, measles, mumps, Norwalk virus, poliomyelitis, rabies. Rift Valley fever, vaccinia, virus diseases (plants), and yellow fever. 

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

Famciclovir is an oral prodrug of penciclovir, a selective antiviral drug with activity against Varicella zoster virus. Herpes simplex virus types 1 and 2, and Epstein-Barr virus, as well as human hepatitis B virus. 

Modification other atoms or groups. Besides fluorine atoms, other atoms (such as C, N and O) and groups are also used to produce novel sugar-modified nucleoside monophosphates. 2-C-Methyl nucleosides are potential candidates with activity against Hepatitis C virus. Leisvuori et al ° prepared 3,5-cyclic phosphates (25a) and 3,5-cyclic thiophosphates (25h) of 2-C-methyl ribonucleosides as potential antiviral drugs. 

Deval J, D Abramo CM, GOtte M (2006) Selective excision of non-obUgate chain-terminators by the hepatitis C virus NS5B polymerase. In 16th international HIV Drug Resistance workshop, Sitges, Spain, June 13-17, 2006. Antivir Ther 11 Suppl 1 S3 (abstract no 1)... 

In this chapter we describe the current insights into the evolution of viruses under pressure of antiviral therapy and the potential impact on viral fimess. As most recent work in this field has been done in the field of human immunodeficiency virus (HIV), we use the evolution of this virus as the basis for the chapter. Subsequently, we describe resistance evolution for Hepatitis B virus (HBV), where large progress has been made in recent years. Furthermore, we describe the resistance development for Hepatitis C virus (HCV), for which a very active drug development program is undertaken by several pharmaceutical companies. Finally, we discuss resistance evolution for Influenza. 

HavUr DV, Richman DD (1996) Viral dynamics of HIV implications for drug development and therapeutic strategies. Ann Intern Med 124(11) 984—994 Hinrichsen H, Benhamou Y, Wedemeyer H, Reiser M, Sentjens RE, Calleja JL, Foms X, Erhardt A, Cronlein J, Chaves RL, Yong CL, Nehmiz G, Steinmann GG (2004) Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype I patients. Gastroenterology 127(5) 1347-1355... 

In pharmacology, two adamantane derivatives. Amantadine (1-adamanta-neamine hydrochloride) and Rimantadine (a-methyl-1-adamantane methyla-mine hydrochloride) (see Fig. 24), have been well known because of their antiviral activity [129]. The main application of these drugs is prophylaxis (treatment to prevent the onset of a particular disease) and treatment of influenza-A viral infections. They are also used in the treatment of parkinsonism and inhibition of hepatitis-C virus. Memantine (1-amino-3,5-dimethyladaman-tane) (see Fig. 24) has been reported effective in slowing the progression of Alzheimer s disease [130]. 

The antiviral activity spectrum of the ddN analogues should, in principle, extend to all retroviruses as well as hepadnaviruses [i.e., hepatitis B virus (HBV)], since HBV, like retroviruses, replicates through an RNA template-driven RT process. Indeed, various ddN analogues (particularly, the L-enantiomeric forms 3TC, FTC, and L-DDC) have been shown to inhibit HBV replication [36-38]. Consequently, 3TC is, at present, pursued as a potential drug candidate for the treatment of both HIV and HBV infections. 

Antiviral Efficacy and Clinical Use. Ribavirin (Vira-zole) is active against several RNA and DNA viruses, including respiratory syncytial virus (RSV).106 Clinically, this drug is used to treat severe RSV pneumonia in infants and young children,106 and RSV in certain adult populations, including the elderly, people with cardiopulmonary problems, and people with a compromised immune system.29 Ribavirin may also be useful as a secondary agent in the treatment of influenza A and B in young adults. The combination of ribavirin and interferons (see section on Interferons, later) is often the treatment of choice in chronic hepatitis C infection.30 72... 

---