Viruses antiviral drugs

Picornaviruses construct their shells from 60 copies each of three different polypeptide chains. These 180 subunits are arranged within the shell in a manner very similar to the 180 identical subunits of bushy stunt virus. In some picornaviruses there are protrusions around the fivefold axes, which are surrounded by deep "canyons." In rhinoviruses, the canyons form the virus s attachment site for protein receptors on the surface of the host cells, and they are adjacent to cavities that bind antiviral drugs. 

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. 

Fig. 3 Stepwise development of antiviral resistance. Because of the rapid mutation rate of viruses, the virus population before treatment (a) contains variants, which display by chance a low level of resistance to the drug (indicated by the darker hue). Treatment with suboptimal levels of an antiviral drug (b) creates a bottleneck, which selects for these variants (c). These can further replicate in the presence of the drug and thereby acquire additional mutations, leading to resistant variants with enhanced replicative fitness (d)...

Baltimore D (1971) Expression of animal virus genomes. Bacteriol Rev 35 235-241 Baltimore D (1988) Gene therapy. Intracellular immunization. Nature 335 395-396 Bauer DJ (1985) A history of the discovery and clinical application of antiviral drugs. Br Med Bull... 

Abstract This review provides an overview of the development of viral protease inhibitors as antiviral drugs. We concentrate on HlV-1 protease inhibitors, as these have made the most significant advances in the recent past. Thus, we discuss the biochemistry of HlV-1 protease, inhibitor development, clinical use of inhibitors, and evolution of resistance. Since many different viruses encode essential proteases, it is possible to envision the development of a potent protease inhibitor for other viruses if the processing site sequence and the catalytic mechanism are known. At this time, interest in developing inhibitors is Umited to viruses that cause chronic disease, viruses that have the potential to cause large-scale epidemics, or viruses that are sufQciently ubiquitous that treating an acute infection would be... 

McCullers JA (2005) Antiviral therapy of influenza. Expert Opin Investig Drugs 14 305-312 McCullers JA (2006) The chnical need for new antiviral drugs directed against influenza virus. J Infect Dis 193 751-753... 

The identification of inhibitors of virus subunit assembly has been an objective of virologists for several years but it is only recently that papers have been published that demonstrate the validity of this approach to antiviral chemotherapy. It is hoped that the information provided by the compounds described above will provide the foundation for the generation of potent antiviral drugs to combat diseases caused by HIV, HBV and other viruses. 

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... 

Activities of 748 (FIAC), 758 (FMAU), and related compounds against several viruses were compared, " and the combined effects of 748 (FIAC) and 758 (FMAU) with other antiviral drugs, or with cyclophosphamide (for FMAU), an immunosuppressive agent, were examined. 

Lewis W, Dalakas MC (1995) Mitochondrial toxicity of antiviral drugs. Nat Med 1(5) 417 22 Lewis W, Day BJ et al (2003) Mitochondrial toxicity of NRTI antiviral drugs an integrated cellular perspective. Nat Rev Drug Discov 2(10) 812-822 Lin-Greenberg A, Taneja-Uppal N (1987) Dysautonomia and infection with the human immunodeficiency virus. Ann Intern Med 106(1) 167... 

Albumin. Albumin is available in highly pure and uniform form, and exhibits low toxicity and good biological stability. It has been used as a carrier for methotrexate and a variety of antiviral drugs [amantadine, fioxuridine (5-fluorodeoxyuridine), and cytar-abine (cytosine arabinoside)] to treat macrophage tumors and infections caused by DNA viruses growing in macrophages. Heavily modified albumins are known... 

LAIV should not be administered until 48 hours after influenza antiviral therapy has stopped, and influenza antiviral drugs should not be administered for 2 weeks after the administration of LAIV because the antiviral drugs inhibit influenza virus replication. 

The two classes of antiviral drugs available for treatment of influenza are the same as those available for prophylaxis and include the adamantanes, amantadine and rimantadine, and the neuraminidase inhibitors, oseltamivir and zanamivir. Because of widespread resistance to the adamantanes among influenza A viruses in the United States, amantadine and rimantadine are not recommended for treatment of influenza until susceptibility can be reestablished. 

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