Ligand-Based and Structured-Based In Silico Repurposing Approaches to Predict Inhibitors of SARS-CoV-2 Mpro Protein

• Main Authors: Alfredo Juárez-Saldívar, Edgar E. Lara-Ramírez, Francisco Reyes-Espinosa, Alma D. Paz-González, Juan Carlos Villalobos-Rocha, Gildardo Rivera
• Format: Article
• Language: English
• Published: Österreichische Apotheker-Verlagsgesellschaft m. b. H. 2020-11-01
• Series: Scientia Pharmaceutica
• Subjects: SARS-CoV-2; docking; virtual screening; repurposing
• Online Access: https://www.mdpi.com/2218-0532/88/4/54

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a coronavirus that causes the pandemic Coronavirus Disease 2019 (COVID-19). There is no current specific treatment for this new coronavirus. In this study, we employed a virtual screening repurposing strategy to search for potential SARS-CoV-2 Mpro inhibitors. The databases PDB, ChEMBL, BindingDB and DrugBank were queried with several filtering steps based on ligand-based and structure-based approaches. As a result, we obtained 58 molecules (37 from ChEMBL and 21 from DrugBank) that potentially inhibit SARS-CoV-2 Mpro. These molecules have on their chemical structure functional groups that favor stronger docking scores than the inhibitor N3. Several of these molecules are reported experimentally as SARS-CoV Mpro inhibitors. Hence, a combined virtual screening strategy allowed finding chemical compounds with a high potential for the inhibition of SARS-CoV-2 Mpro.