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Discovery of Novel Neuraminidase Inhibitors by Structure-Based Virtual Screening, Structural Optimization, and Bioassay.

ABSTRACT: Neuraminidase (NA) is a significant therapeutic target for treating influenza. In this study, a new lead NA inhibitor AN-329/10738021 was discovered by structure-based virtual screening, molecular dynamics simulations, and bioassay validation. Optimization of lead AN-329/10738021, which holds a novel scaffold of N'-benzylidene benzohydrazone, leads to discovery of some novel NA inhibitors Y-1-Y-11. Compound Y-1 exerts the best inhibition activity (IC₅₀ = 0.21 ?M) against NA, which is better than oseltamivir carboxylate (OSC) (IC₅₀ = 3.04 ?M) and lead AN-329/10738021 (IC₅₀ = 1.92 ?M). Molecular docking analysis indicates that the good potency of Y-1 may be ascribed to the elongation of the benzylidene moiety of the molecule to the 430-cavity. The results of this study may offer useful reference for development of novel NA inhibitors.

SUBMITTER: Yu R

PROVIDER: S-EPMC6912870 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Discovery of Novel Neuraminidase Inhibitors by Structure-Based Virtual Screening, Structural Optimization, and Bioassay.

Yu Rao R Cheng Li Ping LP Li Meng M Pang Wan W

ACS medicinal chemistry letters 20191125 12

Neuraminidase (NA) is a significant therapeutic target for treating influenza. In this study, a new lead NA inhibitor AN-329/10738021 was discovered by structure-based virtual screening, molecular dynamics simulations, and bioassay validation. Optimization of lead AN-329/10738021, which holds a novel scaffold of N'-benzylidene benzohydrazone, leads to discovery of some novel NA inhibitors Y-1-Y-11. Compound Y-1 exerts the best inhibition activity (IC<sub ...[more]

PMID: 31857844

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