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Bioorg Med Chem Lett. 2019 Feb 26. pii: S0960-894X(19)30111-8. doi: 10.1016/j.bmcl.2019.02.027. [Epub ahead of print]
Identification, design and synthesis of novel pyrazolopyridine influenza virus nonstructural protein 1 antagonists.
Patnaik S1, Basu D2, Southall N3, Dehdashti S3, Wan KK3, Zheng W3, Ferrer M3, Taylor M3, Engel DA4, Marugan JJ5.
Author information
Abstract
Nonstructural protein 1 (NS1) plays a crucial function in the replication, spread, and pathogenesis of influenza virus by inhibiting the host innate immune response. Here we report the discovery and optimization of novel pyrazolopyridine NS1 antagonists that can potently inhibit influenza A/PR/8/34 replication in MDCK cells, rescue MDCK cells from cytopathic effects of seasonal influenza A strains, reverse NS1-dependent inhibition of IFN-β gene expression, and suppress the slow growth phenotype in NS1-expressing yeast. These pyrazolopyridines will enable researchers to investigate NS1 function during infection and how antagonists can be utilized in the next generation of treatments for influenza infection.
Copyright ? 2019 Elsevier Ltd. All rights reserved.
KEYWORDS:
Antagonist; Antiviral; Influenza; NS1; Pyrazolopyridine
PMID: 30852083 DOI: 10.1016/j.bmcl.2019.02.027
Identification, design and synthesis of novel pyrazolopyridine influenza virus nonstructural protein 1 antagonists.
Patnaik S1, Basu D2, Southall N3, Dehdashti S3, Wan KK3, Zheng W3, Ferrer M3, Taylor M3, Engel DA4, Marugan JJ5.
Author information
Abstract
Nonstructural protein 1 (NS1) plays a crucial function in the replication, spread, and pathogenesis of influenza virus by inhibiting the host innate immune response. Here we report the discovery and optimization of novel pyrazolopyridine NS1 antagonists that can potently inhibit influenza A/PR/8/34 replication in MDCK cells, rescue MDCK cells from cytopathic effects of seasonal influenza A strains, reverse NS1-dependent inhibition of IFN-β gene expression, and suppress the slow growth phenotype in NS1-expressing yeast. These pyrazolopyridines will enable researchers to investigate NS1 function during infection and how antagonists can be utilized in the next generation of treatments for influenza infection.
Copyright ? 2019 Elsevier Ltd. All rights reserved.
KEYWORDS:
Antagonist; Antiviral; Influenza; NS1; Pyrazolopyridine
PMID: 30852083 DOI: 10.1016/j.bmcl.2019.02.027