In silico analysis of potential SARS-CoV-2 main protease inhibitors Nelfinavir and Epirubicin

Published: 21 October 2020| Version 3 | DOI: 10.17632/46z3w8y9pt.3


Inhibiting the main proteasome of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) may serve as a treatment option for patients suffering from COVID-19. Inhibition of the main proteasome (SARS-CoV-2 Mpro) may improve patient outcomes and recovery through blocking viral replication and assembly. A literature review of potential drug treatments for COVID-19 included Nelfinavir, an HIV antiviral, and Epirubicin, an anthracycline and topoisomerase inhibitor. The mechanism of action for both drugs includes binding to SARS-CoV-2 Mpro. These data highlight in-silico binding pose energy predictions of SARS-CoV-2 Mpro (receptor) each of the two drug targets (ligands) using a Generic Evolutionary Method for Molecular Docking (iGEMDOCK). In-silico screening provides highly accurate, reproducible complex-ligand binding affinity prediction data. These data are derived from a population size of 200 and 70 docking generation trials. The 3-D Protein Data Bank (PDB) structure of the main proteasome (SARS-CoV-2 Mpro) for this investigation was derived from the RCSB Protein Data Bank (PDB ID: 6LU7). The 3-D structures of Nelfinavir and Epirubicin were derived from the PubChem database (PubChem CIDs 64143, 41867 respectively). The 3-D structures were converted from 3D conformer SDF files to Protein Data Bank (PDB) formatting through OpenBabble. The data show Nelfinavir as outcompeting Epirubicin in binding to the main proteasome (SARS-CoV-2 Mpro). The complex formation with Nelfinavir was more energetically favorable than that with Epirubicin. The data include relevant binding site residues and energy values, in units of kcal/mol. A composite of van der Waals forces, hydrogen bonding, and electrostatic charge provide the energy values.



Brown University


Computational Chemistry Application, Protease Inhibitor, Severe Acute Respiratory Syndrome Coronavirus 2