Synonyms: Dectova® | GG-167 | GG167 | GR-121167 | GR-121167X | ZMR
zanamivir is an approved drug (FDA (1999), EMA (2019))
Compound class:
Synthetic organic
Comment: Zanamivir (GG167) is a sialic acid-analogue that is used as an antiviral drug. Mechanistcally it inhibits the neuraminidases of both influenza A and B, enzymes that cleave sialic acid residues from host membrane-bound glycoproteins to increase both infection and release of new virus particles from the infected respiratory epithelium. Oseltamivir also belongs to this class of anti-influenza drugs.
A combination of zanamivir and oseltamivir is reported to inhibit mammalian neuraminidase 1 (NEU1) which has the effect of reducing neutrophil overactivation in response to severe viral infection [1]. It is proposed that pharmacological modulation of human NEU1 may represent a novel intervention to dampen neutrophil dysfunction (and the associated tissue damage) during severe infections, as observed in COVID-19. |
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References |
1. de Oliveira Formiga R, Amaral FC, Souza CF, Mendes DAGB, Wanderley CWS, Lorenzini CB, Santos AA, Antônia J, Faria LF, Natale CC et al.. (2023)
Neuraminidase is a host-directed approach to regulate neutrophil responses in sepsis and COVID-19. Br J Pharmacol, 180 (11): 1460-1481. [PMID:36526272] |
2. Krueger AC, Xu Y, Kati WM, Kempf DJ, Maring CJ, McDaniel KF, Molla A, Montgomery D, Kohlbrenner WE. (2008)
Synthesis of potent pyrrolidine influenza neuraminidase inhibitors. Bioorg Med Chem Lett, 18 (5): 1692-5. [PMID:18242993] |
3. Richards MR, Guo T, Hunter CD, Cairo CW. (2018)
Molecular dynamics simulations of viral neuraminidase inhibitors with the human neuraminidase enzymes: Insights into isoenzyme selectivity. Bioorg Med Chem, 26 (19): 5349-5358. [PMID:29903413] |
4. Wen WH, Wang SY, Tsai KC, Cheng YS, Yang AS, Fang JM, Wong CH. (2010)
Analogs of zanamivir with modified C4-substituents as the inhibitors against the group-1 neuraminidases of influenza viruses. Bioorg Med Chem, 18 (11): 4074-84. [PMID:20452227] |