P-ISSN 2587-2400 | E-ISSN 2587-196X
Ejmo Kapak
EJMO Volume : 5 Issue : 2 Year : 2021
EJMO. 2020; 4(4): 336-348 | DOI: 10.14744/ejmo.2020.91768

In Silico Identification of Potential Inhibitors of the Main Protease of SARS-CoV-2 Using Combined Ligand-Based and Structure-Based Drug Design Approach

Bimal Debnath1, Apu Kr Saha2, Samhita Bhaumik3, Sudhan Debnath4
1Department of Forestry and Biodiversity, Tripura University, Suryamaninagar, Tripura, 799022, India, 2Department of Mathematics, National Institute of Technology, Agartala, Tripura, 799046, India, 3Department of Chemistry, Women's College, Agartala, Tripura, 799001, India, 4Department of Chemistry, MBB College, Agartala, Tripura, 799004, India,

Objectives: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a serious global threat. At the time of writing, there are no specific therapeutic agents or vaccines to combat this disease. This study was designed to identify the SARS-CoV-2 main protease inhibitors using drug molecule information retrieved from DrugBank 5.0 (Wishart et al.) Methods: A set of common pharmacophores were generated from a series of 22 known SARS-CoV inhibitors. The best pharmacophore used for virtual screening (VS) of DrugBank using the Phase module followed by structure-based virtual screening (VS) using Glide (Release 2020-1; Schrödinger LLC, New York, NY, USA) with SARS-CoV-2 main protease and 50 ns molecular dynamics (MD) simulation studies. Results: Six hits were selected based on the fitness score, extra-precision Glide score, and binding affinity with the main protease (Mpro). The predicted inhibitor constant (Ki) values of the 3 best hits, DB03777, DB06834, and DB07456, were 0.8176, 0.2148, and 0.1006 ?M, respectively. An MD simulation of DB07456 and DB13592 with the Mpro demonstrated stable protein-ligand complexes. Conclusion: The selected inhibitors displayed a similar type of binding interaction with co-ligands and remdesivir, and the predicted Ki values of 2 inhibitors were found to be superior to remdesivir. These selected hits may be used for further in vitro and in vivo studies against the SARS-CoV-2 Mpro. Keywords: COVID-19, DrugBank, molecular docking, molecular dynamics, pharmacophore, SARS-CoV-2, virtual screening


Cite This Article

Debnath B, Saha A, Bhaumik S, Debnath S. In Silico Identification of Potential Inhibitors of the Main Protease of SARS-CoV-2 Using Combined Ligand-Based and Structure-Based Drug Design Approach. EJMO. 2020; 4(4): 336-348

Corresponding Author: Sudhan Debnath

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