tetano
Editor, Senior Moderator
hem Biol Drug Des
. 2025 Dec;106(6):e70212.
doi: 10.1111/cbdd.70212. 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
Timoteo Delgado-Maldonado[SUP] 1 [/SUP], Alonzo González-González[SUP] 1 [/SUP], Adriana Moreno-Rodríguez[SUP] 2 [/SUP], Guadalupe Rojas-Verde[SUP] 3 [/SUP], Alma D Paz-Gonzalez[SUP] 1 [/SUP], Debasish Bandyopadhyay[SUP] 4 [/SUP], Gildardo Rivera[SUP] 1 [/SUP]
Affiliations
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 (IC[SUB]50[/SUB] = 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 (CC[SUB]50[/SUB] > 200 μM). Therefore, Eu-1 is a candidate compound for further SARS-CoV-2 preclinical experiments.
Keywords: ACE2; SARS‐CoV‐2; molecular docking; natural products; spike protein; viral attachment.
. 2025 Dec;106(6):e70212.
doi: 10.1111/cbdd.70212. 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
Timoteo Delgado-Maldonado[SUP] 1 [/SUP], Alonzo González-González[SUP] 1 [/SUP], Adriana Moreno-Rodríguez[SUP] 2 [/SUP], Guadalupe Rojas-Verde[SUP] 3 [/SUP], Alma D Paz-Gonzalez[SUP] 1 [/SUP], Debasish Bandyopadhyay[SUP] 4 [/SUP], Gildardo Rivera[SUP] 1 [/SUP]
Affiliations
- PMID: 41343336
- DOI: 10.1111/cbdd.70212
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 (IC[SUB]50[/SUB] = 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 (CC[SUB]50[/SUB] > 200 μM). Therefore, Eu-1 is a candidate compound for further SARS-CoV-2 preclinical experiments.
Keywords: ACE2; SARS‐CoV‐2; molecular docking; natural products; spike protein; viral attachment.