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Zanamivir (INN) (IPA: ) is a neuraminidase inhibitor used in the treatment of and prophylaxis of both Influenzavirus A and Influenzavirus B. Zanamivir was the first neuraminidase inhibitor commercially developed. It is currently marketed by GlaxoSmithKline under the trade name Relenza.
Development
Zanamivir was developed in 1989 by scientists at the Australian biotechnology company Biota, working in conjunction with the CSIRO and the Victorian College of Pharmacy. The development was part of Biota's ongoing program to develop antiviral agents through rational drug design.
The strategy relied on the availability of the crystal structure of influenza neuraminidase which was achieved by x-ray crystallography. It was known as far back as 1974 that 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA), a sialic acid analogue, was an inhibitor of neuraminidase.Meindl P, Bodo G, Palese P, Schulman J, Tuppy H. Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. Virology 1974;58(2):457-463. PMID 4362431 Using the crystal structure of neuraminidase and DANA as a starting point, the researchers employed a computer-aided process to attempt to design a molecule which better fitted (and therefore inhibited) the active site of neuraminidase. Zanamivir, a transition-state analogue inhibitor of neuraminidase, was the result.von Itzstein M, Wu W-Y, Kok GB, Pegg MS, Dyason JC, Jin B, et al. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 1993;363(6428):418-423. PMID 8502295
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