Disease relevance of Zanamavir

• OBJECTIVE--The current study evaluated whether intranasal administration of the sialic acid analog 4-guanidino-Neu5Ac2en (GG167), an inhibitor of influenza virus neuraminidase, was effective and safe in either preventing or treating experimental human influenza [1].
• Characterization of mutants of influenza A virus selected with the neuraminidase inhibitor 4-guanidino-Neu5Ac2en [2].
• Human parainfluenza virus type 3 HN-receptor interaction: effect of 4-guanidino-Neu5Ac2en on a neuraminidase-deficient variant [3].
• 4-Guanidino-Neu5Ac2en inhibited plaque formation by laboratory-passaged strains of influenza A and B viruses, with 50% inhibitory concentrations ranging from 0.005 to 0.014 microM [4].
• Effects of the neuraminidase inhibitor zanamavir on otologic manifestations of experimental human influenza [5].

High impact information on Zanamavir

• Zanamivir (4-guanidino-Neu5Ac2en [4-GU-DANA]) inhibits not only the neuraminidase activity but also the receptor interaction of the human parainfluenza virus type 3 (HPIV3) hemagglutinin-neuraminidase (HN), blocking receptor binding and subsequent fusion promotion [6].
• Catalytic and framework mutations in the neuraminidase active site of influenza viruses that are resistant to 4-guanidino-Neu5Ac2en [7].
• Mutations (Asn-->Ser) at amino acids 145 and 150 were also found in the hemagglutinin gene of the B/HK/8/73 (HG) virus resistant to 4-guanidino-Neu5Ac2en [8].
• The virus is 1000-fold less sensitive to the 4-guanidino-Neu5Ac2en in a plaque assay, but only 10-fold less sensitive to 4-amino-Neu5Ac2en [9].
• The cellular interactions of P. falciparum were examined for their sensitivity to 4-guanidino-2,3-didehydro-D-N-acetyl neuraminic acid (4-guanidino Neu5Ac2en), a potent inhibitor of influenza virus sialidase [10].

Anatomical context of Zanamavir

• Anti-influenza virus activity of the neuraminidase inhibitor 4-guanidino-Neu5Ac2en in cell culture and in human respiratory epithelium [11].

Associations of Zanamavir with other chemical compounds

• We reported previously that 4-guanidino-neu5Ac2en (4-GU-DANA) and related sialic acid-based inhibitors of HPF3 neuraminidase activity also inhibit HN-mediated receptor binding and fusion processes not involving neuraminidase activity [3].

Analytical, diagnostic and therapeutic context of Zanamavir

• The development of viral resistance to the neuraminidase (NA) inhibitor, 4-guanidino-Neu5Ac2en, of influenza viruses was studied by serial passage of A/Turkey/Minnesota/833/80 (H4N2) in Madin-Darby canine kidney cells in the presence of increasing concentrations of inhibitor [2].
• Selection of influenza A and B viruses for resistance to 4-guanidino-Neu5Ac2en in cell culture [12].
• The sialidase inhibitor 4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid (4-guanidino-Neu5Ac2en), designed with computer assistance and knowledge of the crystal structure of influenza virus neuraminidase, has shown antiviral effects in animal models of human influenza (M. von Itzstein et al., Nature, 363, 418-423, 1993) [13].
• Determination of the novel sialic acid analog GG167 (GR121167X) in human urine by liquid chromatography: direct injection with column switching [14].
• The anti-influenza activity of the neuraminidase inhibitor 4-guanidino-Neu5Ac2en (4-G-NAc) was determined in Madin-Darby canine kidney (MDCK) cells by yield reduction and ELISA and in explants of human respiratory epithelium by yield reduction [11].

References