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Targeting Human Parainfluenza Virus Type-1 Haemagglutinin-Neuraminidase with Mechanism-Based Inhibitors.
Eveno, Tanguy; Dirr, Larissa; El-Deeb, Ibrahim M; Guillon, Patrice; von Itzstein, Mark.
Afiliação
  • Eveno T; Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia. Tanguy.eveno@griffithuni.edu.au.
  • Dirr L; Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia. L.dirr@griffith.edu.au.
  • El-Deeb IM; Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia. I.el-deeb@griffith.edu.au.
  • Guillon P; Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia. p.guillon@griffith.edu.au.
  • von Itzstein M; Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia. m.vonitzstein@griffith.edu.au.
Viruses ; 11(5)2019 05 05.
Article em En | MEDLINE | ID: mdl-31060278
Human parainfluenza virus (hPIV) infections are a major cause of respiratory tract illnesses in children, with currently no available vaccine or drug treatment. The surface glycoprotein haemagglutinin-neuraminidase (HN) of hPIV has a central role in the viral life cycle, including neuraminic acid-recognising receptor binding activity (early stage) and receptor-destroying activity (late stage), which makes it an ideal target for antiviral drug disovery. In this study, we showed that targeting the catalytic mechanism of hPIV-1 HN by a 2α,3ß-difluoro derivative of the known hPIV-1 inhibitor, BCX 2798, produced more potent inhibition of the neuraminidase function which is reflected by a stronger inhibition of viral replication. The difluorosialic acid-based inhibitor efficiently blocked the neuraminidase activity of HN for a prolonged period of time relative to its unsaturated neuraminic acid (Neu2en) analogue, BCX 2798 and produced a more efficient inhibition of the HN neuraminidase activity as well as in vitro viral replication. This prolonged inhibition of the hPIV-1 HN protein suggests covalent binding of the inhibitor to a key catalytic amino acid, making this compound a new lead for a novel class of more potent hPIV-1 mechanism-based inhibitors.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteína HN / Vírus da Parainfluenza 1 Humana / Inibidores Enzimáticos Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteína HN / Vírus da Parainfluenza 1 Humana / Inibidores Enzimáticos Idioma: En Ano de publicação: 2019 Tipo de documento: Article