School of Integrative Biological & Chemical Sciences Faculty Publications

In Silico and In Vitro Identification of New Eugenol Derivatives as Inhibitors of the Spike SARS-CoV-2 Protein Interaction With the ACE2 Host Receptor

Document Type

Article

Publication Date

12-2025

Abstract

Coronavirus Disease-2019 (COVID-19) caused by SARS-CoV-2 remains a serious health concern worldwide. Inhibitors of the protein-protein interaction (iPPI) between the SARS-CoV-2 spike protein (S) and human Angiotensin-Converting Enzyme-2 (ACE2) are promising as potential antiviral agents. This study aimed to identify and evaluate novel compounds as inhibitors of the S receptor-binding domain (RBD) and ACE2 interaction through Eugenol- and Structure-Based virtual screening approaches. The hit compounds were corroborated as protein-protein interaction inhibitors using an ELISA-based enzyme assay. Molecular docking and molecular dynamics (MD) studies of the selected compounds showed that they maintained a molecular interaction and stability (RMSD fluctuations less than 4 Å) with essential residues of the S protein. The best compound, Eu-1 (IC50 = 16 μM), prevented the interaction between the S protein and ACE2 receptor efficiently with an 83.7% inhibition at 50 μM. In addition, Eu-1 had an adequate value of cytotoxicity (CC50 > 200 μM). Therefore, Eu-1 is a candidate compound for further SARS-CoV-2 preclinical experiments.

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© 2025 John Wiley & Sons Ltd.

https://onlinelibrary.wiley.com/share/MASBD6XMF5YGSX5FIFEJ?target=10.1111/cbdd.70212

Publication Title

Chemical Biology & Drug Design

DOI

10.1111/cbdd.70212

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