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Innovative Medicines & Omics

ORIGINAL RESEARCH ARTICLE
In silico analysis for the proposal of new drugs

against the phosphoprotein nucleocapsid
of the severe acute respiratory syndrome

coronavirus 2 virus

2†
1†
Amanda Bubula de Souza , Leonardo Pereira de Araújo ,
1
Amanda Almeida Morais , Leandro Marcos Santos ,
1
1
Yana Cristina Albanez Santos , Cássia Milene Ribeiro Lopes ,
1
3
Paulo Vinicius Sanches Daltro de Carvalho , Syed Shah Hassan * ,
4
and Nelson José Freitas da Silveira *
1
1 Laboratory of Molecular Modeling and Computer Simulation, Federal University of Alfenas
(UNIFAL), Alfenas, Minas Gerais, Brazil
2 Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas (UNIFAL),
Alfenas, Minas Gerais, Brazil
3 Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz), Rio
de Janeiro, RJ, Brazil
4 International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
† These authors contributed equally Abstract
to this work.
*Corresponding authors: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory
Nelson José Freitas da Silveira syndrome coronavirus 2 (SARS-CoV-2), which began in late 2019, has resulted in
(nelson.silveira@unifal-mg.edu.br)
Syed Shah Hassan approximately seven million deaths worldwide. This underscores the urgent need
(hassanchemist83@iccs.edu) for vaccine and drug development. In silico techniques, especially molecular docking,
provide promising means for discovering new treatments. This study aimed to
Citation: de Souza AB, de
Araújo LP, Morais AA, et al. In silico identify novel compounds with potential activity against the nucleocapsid protein of
analysis for the proposal of new SARS-CoV-2 using drug repositioning and bioisosterism techniques. We performed
drugs against the phosphoprotein molecular docking with 20,115 compounds from the BindingDB database. The protein,
nucleocapsid of the severe acute
respiratory syndrome coronavirus obtained from the Protein Data Bank (PDB ID: 6WZQ), was prepared using MGLTools
2 virus. Innov Med Omics. software, including protonation and removal of co-crystallized ligands and water
2024;1(1):115-124. molecules. We defined the binding site at the protein’s active site and used AutoDock
doi: 10.36922/imo.3731
Vina software for molecular docking, ranking the results based on relative binding
Received: May 21, 2024 energy. Interactions were visualized using Pymol and LigPlot+ software, focusing on
Accepted: July 8, 2024
Published Online: August 22, 2024 hydrogen bonds and hydrophobic interactions. Compound BDBM6732 showed the
most favorable binding energy (−13.4 kcal/mol), similar to the control compound
Copyright: © 2024 Author(s).
This is an Open-Access article suramin (−13.3 kcal/mol), but it was predicted to carry risks for hepatotoxicity and
distributed under the terms of the mutagenesis. We generated bioisosteres, resulting in two candidate analog compounds
Creative Commons Attribution with superior affinity to four compounds referenced in the scientific literature, two of
License, permitting distribution,
and reproduction in any medium, which had their activity validated in in vivo testing. These results suggest that the two
provided the original work is analogs may potentially combat SARS-CoV-2 by binding to the nucleocapsid protein.
properly cited. However, validation in both in vitro and in vivo settings is essential.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in Keywords: Molecular docking; SARS-CoV-2; Nucleocapsid; Bioinformatics; Analogous
published maps and institutional compound
affiliations.

Volume 1 Issue 1 (2024) 115 doi: 10.36922/imo.3731