Identification of inhibitors of SARS-Cov-2 -S protein and human ACE2 interaction based on secondary metabolites from Rose water: molecular docking approach

Document Type : Research Article


1 Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran

2 Department of Chemistry, Faculty of Science, University of Qom, Qom, Iran

3 Nutringredientes Research Center, Federal Institute of Education, Science and Technology (IFCE), Brazil



Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new member of the Betacoronavirus family that has led to a pandemic in g recent years. It is well documented that the Receptor Binding Domain (RBD) of the S protein (spike glycoprotein) of SARS-CoV-2 binds to the human Angiotensin-Converting Enzyme 2 (ACE2) receptor to enter lower respiratory tract epithelial cells. Thus, inhibition of SARS-CoV-2-RBD/ACE2 interactions presents an interesting research challenge. In this study, molecular docking approaches were applied to identify compounds from Rose water secondary metabolites against SARA-CoV2. Subsequently, several Rose water secondary metabolites from Rose water were identified, that had the highest percentages of Rosewater, including Eugenol, Alpha-terpineol, Geraniol, Citronellol, Phenylethyl alcohol, Nerol, and Linalool. Autodock vina software was used to perform docking between selected secondary metabolites and the ACE2 binding site of SARS-CoV-2 -RBD. The docking results were analyzed based on the binding affinity, binding modes, and physicochemical properties. The results indicated that all selected secondary metabolites could bind to RBD; however, Eugenol had the highest binding affinity (-6.0 kcal/mol) compared to Alpha-terpineol (--5.7 kcal/mol), Geraniol (-5.3 kcal/mol), Phenylethyl alcohol (-5.3 kcal/mol), Citronellol (-4.6 kcal/mol),  Nerol (-4.4 kcal/mol), and Linalool (-4.3 kcal/mol). Our Computer Aid Drug Design approach may contribute to the development of new drugs against SARS-CoV-2. However, the effect of these secondary metabolites needs to be evaluated.


Main Subjects

The RBD domain of the SARS-CoV-2-S protein is a crucial domain in binding to the ACE2 receptor; therefore, inhibiting SARS-CoV-2 -S protein and human ACE2 interaction need to be studied. The results of docking and molecular interactions between SARSCoV-2-RBD and selected secondary metabolites of Rose water demonstrated that Eugenol has better binding affinity and conformation compared to Alphaterpineol, Geraniol, Citronellol, Phenylethyl alcohol, Nerol, and Linalool. In addition, the evaluation of physicochemical properties showed that all compounds possessed RO5. However, the efficiency of the selected secondary metabolites requests to survey in vitro and in vivo as well as the obtained results can provide data for the next studies

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