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Updated: Jun 14, 2026

Pharmacophore Modeling for Targets with Extensive Ligand Libraries: A Case Study on SARS-CoV-2 Mpro
Published on: September 26, 2025
Pharmacophore based drug design approach as a practical process in drug discovery
Qingzhi Gao1, Lulu Yang, Yongqiang Zhu
1Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, China. qingzhi@gmail.com
Abstract:
This review summarizes the background and updated progress of pharmacophore based drug design and provides the fundamental approach strategies on both structure based and ligand based pharmacophore approaches. The different programs and methodologies enable the implementation of more accurate and sophisticated pharmacophore model generation and application in drug discovery. This review will discuss and illustrate their advantages in pharmacophore based virtual screening and exemplify the detailed application workflow, which can be easily utilized by pharmaceutical bench work medicinal chemists. Pharmacophore based drug design process includes pharmacophore modeling and validation; pharmacophore based virtual screening, virtual hits profiling and lead identification. Strategies and proven methodologies for pharmacophore modeling are described including common feature and 3D QSAR based pharmacophore generation as well as structure based pharmacophore development. Different virtual screening strategies will be described in this review with detailed case studies for supporting practical applications. Representative success examples of pharmacophore based virtual screening for lead generation will be collected to demonstrate capabilities.
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