Antivirals ribavirin

Ribavirin is not incorporated into the DNA or RNA of either mammalian or viral systems. It has been shown (123), however, that a high dosage of ribavirin given over a prolonged period to Rhesus monkeys results in anemia of red blood cells. This effect is dose related and reversible upon cessation of treatment. Guanosine partially reverses the antiviral effect of ribavirin against certain vimses. 

The nucleotide form of ribavirin does not manifest its antiviral activity simply by lowering the GTP levels, but may indeed participate directly in binding to specific G proteins (124). Ribavirin has recently been studied as an inhibitor of vesicular stomatitis vims and La Crosse vims (125). Of the phosphorylated forms of the dmg, ribavirin-5 -diphosphate was by far the most potent inhibitor of viral repHcation for these two vimses. 

Unlike idoxuridiae, BVdU, and acyclovir, viral strains susceptible to ribavirin have not been found to develop a resistance to the dmg. The resistance against ribavirin is less likely because the dmg exhibits multiple sites of antiviral action. 

Although the stmctures of ribavirin and selenazofutin are similar, they appear to exert their antiviral action at different enzyme sites along the same biochemical pathway. Selenazofutin forms the nicotinamide adenosiae dinucleotide (NAD) analogue, which inhibits IMP dehydrogenase by binding ia place of the NAD cofactor, and hence this potent reduction of guanylate pools is responsible for the antiviral effect of selenazofutin. 

Although the term nucleoside was once limited to the compounds in Table 28.2 and a few others, cunent use is more permissive. Pyrimidine derivatives of D-arabinose, for exfflnple, occur in the free state in certain sponges and are called spongonticleosides. The powerful antiviral drug ribavirin, used to treat hepatitis C and Lassa fever, is a synthetic nucleoside analog in which the base, rather than being a pyrimidine or purine, is a triazole. 

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

Sieczkarski SB, Whittaker GR (2005) Viral entry, Curr Top Microbiol Immunol 285 1-23 Snell NJ (2001). Ribavirin-current status of a broad spectrum antiviral agent. Expert opinion on pharmacotherapy 2 1317-1324... 

It may be possible to increase the utility of our resources to treat influenza virus infection through combinations of antiviral agents with different modes of action (discussed in Cinatl et al. 2007a De Clercq and Neyts 2007). The sialidase inhibitors, for example, may be able to be used in conjunction with the adamantane-based M2 ion channel inhibitors (Govorkova et al. 2004 Ilyushina et al. 2006), with Ribavirin (Smee et al. 2002) or with non-influenza virus specific therapeutics such as anti-inflammatory drugs (Carter 2007). Combination therapy may also reduce the potential of resistance development (Ilyushina et al. 2006). 

In nonresponders to IFN-a-ribavirin, the antiviral effect of boceprevir appeared to be strictly additive to that of pegylated IFN-a2b (Sarrazin et al. 2007). In an ongoing phase II chnical trial, higher doses of boceprevir are being administered to treatment-naive patients, in combination with pegylated IFN-a and ribavirin. 

Gunsar E, Akarca US, Ersoz G, Kobak AC, Karasu Z, Yuce G, liter T, Batur Y (2005) Two-year interferon therapy with or without ribavirin in chronic delta hepatitis. Antivir Ther 10 721-726 Habersetzer E, Boyer N, MarceUin P, Badly F, Ahmed SN, Alam J, Benhamou JP, Trepo C (2000) A pdot study of recombinant interferon beta-la for the treatment of chronic hepatitis C. Liver 20 437 41... 

Ribavirin is a guanosine analog synthesized more than 35 years ago, which possesses broad-spectrum antiviral activity against several RNA and DNA viruses in vitro (Sidwell et al. 1972). When administered as monotherapy in patients with chronic hepatitis C, ribavirin induces a decline of serum alanine aminotransferase (ALT) levels while no effect on sustained virologic response is detectable (Di Bisceglie et al. 1992). 

Hofmann WP, Polta A, Herrmann E, Mihm U, Kronenberger B, Sonntag T, Lohmann V, SchonbergerB, Zeuzem S, Sarrazin C (2007) Mutagenic effect of ribavirin on hepatitis C nonstructural 5B quasispecies in vitro and during antiviral therapy. Gastroenterology I32(3) 92I-930... 

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