Efficient ligand discovery from natural herbs by integrating virtual screening, affinity mass spectrometry and targeted metabolomics

The Analyst
Zhihua WangWenqing Shui

Abstract

Although natural herbs have been a rich source of compounds for drug discovery, identification of bioactive components from natural herbs suffers from low efficiency and prohibitive cost of the conventional bioassay-based screening platforms. Here we develop a new strategy that integrates virtual screening, affinity mass spectrometry (MS) and targeted metabolomics for efficient discovery of herb-derived ligands towards a specific protein target site. Herb-based virtual screening conveniently selects herbs of potential bioactivity whereas affinity MS combined with targeted metabolomics readily screens candidate compounds in a high-throughput manner. This new integrated approach was benchmarked on screening chemical ligands that target the hydrophobic pocket of the nucleoprotein (NP) of Ebola viruses for which no small molecule ligands have been reported. Seven compounds identified by this approach from the crude extracts of three natural herbs were all validated to bind to the NP target in pure ligand binding assays. Among them, three compounds isolated from Piper nigrum (HJ-1, HJ-4 and HJ-6) strongly promoted the formation of large NP oligomers and reduced the protein thermal stability. In addition, cooperative binding between ...Continue Reading

References

Mar 30, 2001·Journal of Chemical Information and Computer Sciences·M HeG Xie
Mar 7, 2009·Journal of Medicinal Chemistry·Josefin RosénTudor I Oprea
Apr 11, 2009·Journal of Chemical Information and Modeling·Tiejun ChengRenxiao Wang
Mar 18, 2010·Angewandte Chemie·Daniel Shiu-Hin ChanDik-Lung Ma
Apr 2, 2010·Nature Reviews. Drug Discovery·Gisbert Schneider
Oct 7, 2011·Journal of the American Chemical Society·Nawaporn Vinayavekhin, Alan Saghatelian
Feb 10, 2012·Journal of Natural Products·David J Newman, Gordon M Cragg
Jan 22, 2013·Expert Opinion on Drug Discovery·Supratik Kar, Kunal Roy
May 28, 2014·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Hui-Peng SongPing Li
Sep 12, 2014·Journal of Chemical Information and Modeling·Tiziano TuccinardiAdriano Martinelli
Sep 17, 2014·Chemical Communications : Chem Comm·Dik-Lung MaChung-Hang Leung
Jan 24, 2015·Nature Reviews. Drug Discovery·Alan L HarveyRonald J Quinn
Jun 30, 2015·Cell Reports·Robert N KirchdoerferErica Ollmann Saphire
Feb 26, 2016·Journal of Medicinal Chemistry·John J Irwin, Brian K Shoichet
Oct 14, 2016·Nature·Edward C HolmesKristian G Andersen

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Citations

Jan 9, 2021·Signal Transduction and Targeted Therapy·Dehua YangMing-Wei Wang
May 15, 2020·Journal of Chemical Information and Modeling·Hao LiangLuhua Lai

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Methods Mentioned

BETA
affinity purification
thermal
Protein Thermal Shift
PCR
fluorescence
thermal shift

Software Mentioned

MSstats
Glide
AutoDock
PeakView
LigPrep
AutoDockTools
AutodDock
AutoDock Vina
Schrödinger
LightCycler® 480

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