Antiviral activities guanosine

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). 

Entecavir is a guanosine nucleoside with strong antiviral activity. It is also effective in lamivudine-resistant patients. After 48 weeks of treatment comprising a daily dose of 0.5 or 1.0 mg, there was elimination of HBV DNA in 25 — 30% and normalization of the transaminases in 60—70% of lamivudine-resistant patients. Tolerance is good. Entecavir-induced mutants were not detected. (173)... 

The synthetic triazole nucleoside, ribavirin (1-beta-D-ribofuranosyl-l,2,4-triazole-3-carboxamide, tribavirin, virazole), has a broad spectrum of antiviral activity, including DNA as well as RNA viruses (1). Ribavirin closely resembles guanosine and is converted intracellu-larly to mono-, di-, and triphosphate derivatives, which inhibit the virally induced enzymes involved in viral nucleic acid synthesis by different mechanisms that are not fully understood (2). Of the DNA viruses, ribavirin is active against Herpes simplex virus and hepatitis B virus among the RNA viruses, good activity has been observed against hepatitis C virus, orthomyxoviruses. 

Oral guanosine analogue with antiviral activity against variety of RNA and DNA viruses. For HCV infections, combination of ribavirin plus interferon improves virologic response compared to interferon monotherapy. 

Oxanosine, a novel guanosine analogue antibiotic has been phosphorylated according to the Yoshikawa procedure to yield (17) and evaluated for in vitro antiviral activity against HIV proliferation. Compound (17) reduced the number of HIV particles in CEM cells to almost the same level as ddl. 

The isothiazolo[4,5-d]pyrimidin-3-yl C-nucleoside analogs of adenine and guanosine, 559 and 560, respectively, were also synthesized (94JOC1912). C-Nucleosides 552,558,559, and 560 were tested for antiviral activity against HIV, HCMV, HSV, and rhinoviruses and found inactive (93JOC5181 94JOC1912). 

Mechanism of Action. The drug is a nueleoside analogue structurally related to guanosine having distinct antiviral activity against HIV-1. Its acts as an inhibitor of viral reverse transcryptase and is under investigation in the treatment of AIDS. 

A Cannizzaro reaction of a protected guanosine-5 -aldehyde was the key step In a synthesis of 4 -(hydro3qrmethyl)guanosine (44). which was devoid of antiviral activity. 9 ... 

C-Acyclic nucleoside analogs of inosine and guanosine 8-[(/ 5)-2,3-dihydroxypropyl]imidazo[l,5-fl]-l,3,5-triazin-4(3//)-ones were synthesized. The route involved the cyclization and rearrangement of 5-acylamino-5-allyl-6-amino-4,5-dihydropyrimidin-4-ones (1122) to 8-allylimidazo[l,5-a]-l,3,5-triazin-4(3//)-ones (1123). Osmium tetroxide hydroxylation gave 1124. None of these analogs showed appreciable antiviral or antitumor cell activity (84NAR263 87MI6). 

Ribavirin is a synthetic guanosine analogue that possesses broad antiviral inhibitory activity against many viruses, including influenza A and B, parainfluenza, RS V, HCV, HIV-1, and various herpesviruses, arenaviruses, and paramyxoviruses. Its exact mechanism of action has not been fully elucidated however, it appears to inhibit the synthesis of viral mRNA through an effect on nucleotide pools. Following absorption, host cell enzymes convert ribavirin to its monophosphate, diphosphate, and triphosphate forms. Ribavirin monophosphate... 

Ribavirin This guanosine analogue was first used experimentally by o. Reichard et al. (1991) and in chronic hepatitis C by J. Andersson et al. (1991). It is rapidly absorbed and distributed in the body, but is excreted slowly (half-life 79 hours). The bioavailability is 45-65%. As a monotherapy, it only leads to a decrease in transaminases and a slight improvement in histological activity. Ribavirin may not exhibit a direct antiviral effect, but can trigger a favourable response to interferon. When combined with IFN, ribavirin proved far more efficacious in chronic hepatitis C (immunomo-dulation ) without any increase in the typical side effects of IFN. (49, 51, 53) (s. p. 707)... 

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