Molecular modeling study of natural products as potential bioactive compounds against SARS-CoV-2.

Autor: Ribeiro R; Department of Chemical Engineering, Military Institute of Engineering, Rio de Janeiro, RJ, Brazil., Botelho FD; Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMCBD), Military Institute of Engineering, Rio de Janeiro, RJ, Brazil., Pinto AMV; Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMCBD), Military Institute of Engineering, Rio de Janeiro, RJ, Brazil., La Torre AMA; Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMCBD), Military Institute of Engineering, Rio de Janeiro, RJ, Brazil., Almeida JSFD; Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMCBD), Military Institute of Engineering, Rio de Janeiro, RJ, Brazil., LaPlante SR; INRS, Centre Armand-Frappier Santé Biotechnologie 531, Boulevard Des Prairies, Laval, QC, Canada., Franca TCC; Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMCBD), Military Institute of Engineering, Rio de Janeiro, RJ, Brazil.; INRS, Centre Armand-Frappier Santé Biotechnologie 531, Boulevard Des Prairies, Laval, QC, Canada.; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic., Veiga-Junior VF; Department of Chemical Engineering, Military Institute of Engineering, Rio de Janeiro, RJ, Brazil., Dos Santos MC; Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMCBD), Military Institute of Engineering, Rio de Janeiro, RJ, Brazil. marcelocarneiro.mcs@gmail.com.
Jazyk: angličtina
Zdroj: Journal of molecular modeling [J Mol Model] 2023 May 22; Vol. 29 (6), pp. 183. Date of Electronic Publication: 2023 May 22.
DOI: 10.1007/s00894-023-05586-5
Abstrakt: Context: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 infection and responsible for millions of victims worldwide, remains a significant threat to public health. Even after the development of vaccines, research interest in the emergence of new variants is still prominent. Currently, the focus is on the search for effective and safe drugs, given the limitations and side effects observed for the synthetic drugs administered so far. In this sense, bioactive natural products that are widely used in the pharmaceutical industry due to their effectiveness and low toxicity have emerged as potential options in the search for safe drugs against COVID-19. Following this line, we screened 10 bioactive compounds derived from cholesterol for molecules capable of interacting with the receptor-binding domain (RBD) of the spike protein from SARS-CoV-2 (SC2Spike), responsible for the virus's invasion of human cells. Rounds of docking followed by molecular dynamics simulations and binding energy calculations enabled the selection of three compounds worth being experimentally evaluated against SARS-CoV-2.
Methods: The 3D structures of the cholesterol derivatives were prepared and optimized using the Spartan 08 software with the semi-empirical method PM3. They were then exported to the Molegro Virtual Docking (MVD®) software, where they were docked onto the RBD of a 3D structure of the SC2Spike protein that was imported from the Protein Data Bank (PDB). The best poses obtained from MVD® were subjected to rounds of molecular dynamics simulations using the GROMACS software, with the OPLS/AA force field. Frames from the MD simulation trajectories were used to calculate the ligand's free binding energies using the molecular mechanics - Poisson-Boltzmann surface area (MM-PBSA) method. All results were analyzed using the xmgrace and Visual Molecular Dynamics (VMD) software.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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