Virtual Screening of Natural Chemical Databases to Search for Potential ACE2 Inhibitors

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 5; p. 1740
• Main Author: Yao, Huiping
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.03.2022; MDPI
• Subjects: ACE2; Angiotensin; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - antagonists & inhibitors; Angiotensin-Converting Enzyme 2 - metabolism; Binding; Binding Sites; Biological Products - chemistry; Biological Products - metabolism; Biological Products - therapeutic use; Cluster analysis; Coronaviruses; COVID-19; COVID-19 - drug therapy; COVID-19 - virology; Databases, Chemical; Diabetes mellitus; Humans; inhibitor; Inhibitors; Lung cancer; Lung diseases; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; Natural products; Ovarian cancer; Peptidyl-dipeptidase A; Protease Inhibitors - chemistry; Protease Inhibitors - metabolism; Protease Inhibitors - therapeutic use; Protein Binding; Proteins; SARS-CoV-2 - isolation & purification; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Strong interactions (field theory); Structure-Activity Relationship; Therapeutic targets; Thermodynamics; virtual screening; Viruses; ACE2; natural products; inhibitor; virtual screening; molecular dynamics simulation
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27051740

The angiotensin-converting enzyme II (ACE2) is a multifunctional protein in both health and disease conditions, which serves as a counterregulatory component of RAS function in a cardioprotective role. ACE2 modulation may also have relevance to ovarian cancer, diabetes, acute lung injury, fibrotic diseases, etc. Furthermore, since the outbreak of the coronavirus disease in 2019 (COVID-19), ACE2 has been recognized as the host receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The receptor binding domain of the SARS-CoV-2 S-protein has a strong interaction with ACE2, so ACE2 may be a potent drug target to prevent the virus from invading host cells for anti-COVID-19 drug discovery. In this study, structure- and property-based virtual screening methods were combined to filter natural product databases from ChemDiv, TargetMol, and InterBioScreen to find potential ACE2 inhibitors. The binding affinity between protein and ligands was predicted using both Glide SP and XP scoring functions and the MM-GBSA method. ADME properties were also calculated to evaluate chemical drug-likeness. Then, molecular dynamics (MD) simulations were performed to further explore the binding modes between the highest-potential compounds and ACE2. Results showed that the compounds 154-23-4 and STOCK1N-07141 possess potential ACE2 inhibition activities and deserve further study.