Work

Ligand‐Based Pharmacophore Modeling and Structure‐Based Virtual Screening for Identifying Potential Therapeutic Agents Targeting the SARS‐CoV‐2 Spike Protein‐ACE2 Receptor Interaction

Year: 2026

Type: article

Abstract: Coronavirus disease (COVID‐19) remains a global health concern due to its high mortality and morbidity. In this study, we combined ligand‐based pharmacophore modeling (LBPM) with structure‐based virtual screening (SBVS) to identify novel inhibitors targeting the SARS‐CoV‐2 spike protein. Ligands from the MolPort database were screened via docking and molecular dynamics simulations at the receptor‐binding domain (RBD). Four compounds showed promising docking scores (–8.7 to –6.4 kcal/mol) and dynamic stability (root mean square deviation < 5 Å). In vitro assays confirmed that compounds C3 (IC 50 = 0.03 µM) and C4 (IC 50 = 10.4 µM) effectively inhibited spike–ACE2 binding with low cytotoxicity (CC 50 > 100 µM). These findings show the efficacy of the LBPM technique and highlight 1H‐pyrazol‐5‐ol derivatives as potential building blocks for developing new antiviral agents against SARS‐CoV‐2.

Source: ChemMedChem

DOI: 10.1002/cmdc.70311

Authors: Timoteo Delgado‐Maldonado, Gilberto Vargas‐Salas, Debasish Bandyopadhyay, Adriana Moreno‐Rodríguez, Eyra Ortiz‐Pérez, Gildardo Rivera

Institutions: Instituto Politécnico Nacional, The University of Texas Rio Grande Valley, Benito Juárez Autonomous University of Oaxaca

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Computational Theory and Mathematics

Field: Computer Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,150