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Arch Virol. 1997 Jul;142(7):1365-1380. doi: 10.1007/s007050050166.

A novel synthetic reversible inhibitor of sialidase efficiently blocks secondary but not primary influenza virus infection of MDCK cells in culture.

Archives of virology

B Barrêre, P A Driguez, J Maudrin, A Doutheau, M Aymard, G Quash

Affiliations

  1. Laboratoire d'Immunochimie, Faculté de Médecine Lyon-Sud, Oullins, France, France.
  2. Laboratoire de Chimie Organique, INSA, Villeurbanne, France, and, France.
  3. Laboratoirede Virologie et Bactériologie, UFR de Médecine, Lyon, France, France.

PMID: 28879398 DOI: 10.1007/s007050050166

Abstract

The sodium salts of 2-difluoromethyl-phenyl-α-ketoside of N-acetyl-neuraminic acid (compound 1) and of 4-difluoromethyl-2-methoxy-phenyl-α-ketoside of N-acetylneuraminic acid (compound 2) were designed as potential mechanism-based inhibitors of sialidase. In vitro both of these compounds competitively inhibited the sialidases of Clostridium perfringens and of influenza virus A/HK/1/68. Inhibition was irreversible with the sialidase of Clostridium perfringens whereas it was reversible with that of A/HK/1/68. Compound 2 did not inhibit the hemagglutinin of the virus but exhibited significant anti-influenza activity when added to the medium of Madin-Darby canine kidney (MDCK) cells infected by influenza virus. In non-infected MDCK cells no inhibition of cellular sialidase was observed. Compound 2 did not block primary infection, but inhibited the release of progeny virus from infected cells. Even after 8 passages in its presence, no resistant strains were detected. Because of its high Ki (8 × 10

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