Zanamivir antiviral activity

The retention of potent enzyme inhibition and in vitro antiviral activity in the presence of functionalisation with relatively long hydrophobic chains at C-7 of zanamivir has been exploited in the development of di- and poly-valent structmes carrying zanamivir (reviewed in Sun 2007). Multivalent presentation of drug may... 

Currently, two classes of drugs are available with antiviral activity against influenza viruses inhibitors of the ion channel activity of the M2 membrane protein, amantadine and rimantadine, and the neuraminidase inhibitors oseltamivir, and zanamivir. H5N1 viruses isolated from poultry and humans in Thailand and Viet Nam in 2004 invariably showed an amantadine-resistance indicating that amantadine treatment is not an option during the ongoing outb-treak in South-East Asia. 

Several carbocylic analogues of zanamivir that have been developed subsequently that display the same antiviral activity as zanamivir. The importance of the first of these, oseltamivir, more familiarly known as Tamiflu , has attracted the attention of academic chemists. Departing briefly from the organizing principle of this book. 

Oseltamivir phosphate is an ethyl ester prodrug that lacks antiviral activity. Oseltamivir carboxylate has an antiviral spectrum and potency similar to that of zanamivir. It inhibits amantadine- and rimantadine-resistant influenza A viruses and some zanamivir-resistant variants. 

CHEMISTRY AND ANTIVIRAL ACTIVITY Zanamivir (4-guanidino-2,4-dideoxy-2, 3-dehydro-/V-acetyl neuraminic acid) is a siaMc acid analog that potently and specifically inhibits the neuraminidases of influenza A and B viruses. Depending on the strain, zanamivir competitively inhibits influenza neuraminidase activity but affects neuraminidases from other pathogens and mammalian sources only at much higher concentrations. Zanamivir inhibits in vitro replication of influenza A and B viruses, including amantadine- and rimantadine-resistant strains and several oseltamivir-resistant variants. 

Antacids do not affect the pharmacokinetics of oseltamivir, and there is no pharmacokinetic interaction between aspirin or paracetamol (acetaminophen) and oseltamivir. Aspirin and a variety of other drugs used for influenza management do not affect the antiviral activity of zanamivir in vitro. 

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