tetano
Editor, Senior Moderator
Mol Biotechnol
. 2023 Jul 25.
doi: 10.1007/s12033-023-00831-x. Online ahead of print. Screening of Potential Inhibitors Targeting the Main Protease Structure of SARS-CoV-2 via Molecular Docking, and Approach with Molecular Dynamics, RMSD, RMSF, H-Bond, SASA and MMGBSA
Aluísio Marques da Fonseca[SUP] 1 [/SUP], Bernardino Joaquim Caluaco[SUP] 2 [/SUP], Junilson Martinho Canjanja Madureira[SUP] 2 [/SUP], Sadrack Queque Cabongo[SUP] 2 [/SUP], Eduardo Menezes Gaieta[SUP] 3 [/SUP], Faustino Djata[SUP] 2 [/SUP], Regilany Paulo Colares[SUP] 2 [/SUP], Moises Maia Neto[SUP] 4 [/SUP], Carla Freire Celedonio Fernandes[SUP] 3 [/SUP], Gabrielle Silva Marinho[SUP] 5 [/SUP], Hélcio Silva Dos Santos[SUP] 6 [/SUP], Emmanuel Silva Marinho[SUP] 5 [/SUP]
Affiliations
Severe Acute Respiratory Syndrome caused by a coronavirus is a recent viral infection. There is no scientific evidence or clinical trials to indicate that possible therapies have demonstrated results in suspected or confirmed patients. This work aims to perform a virtual screening of 1430 ligands through molecular docking and to evaluate the possible inhibitory capacity of these drugs about the M[SUP]pro[/SUP] protease of Covid-19. The selected drugs were registered with the FDA and available in the virtual drug library, widely used by the population. The simulation was performed using the MolAiCalD algorithm, with a Lamarckian genetic model (GA) combined with energy estimation based on rigid and flexible conformation grids. In addition, molecular dynamics studies were also performed to verify the stability of the receptor-ligand complexes formed through analyses of RMSD, RMSF, H-Bond, SASA, and MMGBSA. Compared to the binding energy of the synthetic redocking coupling (-6.8 kcal/mol/RMSD of 1.34 Å), which was considerably higher, it was then decided to analyze the parameters of only three ligands: ergotamine (-9.9 kcal/mol/RMSD of 2.0 Å), dihydroergotamine (-9.8 kcal/mol/RMSD of 1.46 Å) and olysio (-9.5 kcal/mol/RMSD of 1.5 Å). It can be stated that ergotamine showed the best interactions with the M[SUP]pro[/SUP] protease of Covid-19 in the in silico study, showing itself as a promising candidate for treating Covid-19.
Keywords: Coronavirus; Ligand; Molecular docking; Receptor; Virtual screening; covid19.
. 2023 Jul 25.
doi: 10.1007/s12033-023-00831-x. Online ahead of print. Screening of Potential Inhibitors Targeting the Main Protease Structure of SARS-CoV-2 via Molecular Docking, and Approach with Molecular Dynamics, RMSD, RMSF, H-Bond, SASA and MMGBSA
Aluísio Marques da Fonseca[SUP] 1 [/SUP], Bernardino Joaquim Caluaco[SUP] 2 [/SUP], Junilson Martinho Canjanja Madureira[SUP] 2 [/SUP], Sadrack Queque Cabongo[SUP] 2 [/SUP], Eduardo Menezes Gaieta[SUP] 3 [/SUP], Faustino Djata[SUP] 2 [/SUP], Regilany Paulo Colares[SUP] 2 [/SUP], Moises Maia Neto[SUP] 4 [/SUP], Carla Freire Celedonio Fernandes[SUP] 3 [/SUP], Gabrielle Silva Marinho[SUP] 5 [/SUP], Hélcio Silva Dos Santos[SUP] 6 [/SUP], Emmanuel Silva Marinho[SUP] 5 [/SUP]
Affiliations
- PMID: 37490200
- DOI: 10.1007/s12033-023-00831-x
Severe Acute Respiratory Syndrome caused by a coronavirus is a recent viral infection. There is no scientific evidence or clinical trials to indicate that possible therapies have demonstrated results in suspected or confirmed patients. This work aims to perform a virtual screening of 1430 ligands through molecular docking and to evaluate the possible inhibitory capacity of these drugs about the M[SUP]pro[/SUP] protease of Covid-19. The selected drugs were registered with the FDA and available in the virtual drug library, widely used by the population. The simulation was performed using the MolAiCalD algorithm, with a Lamarckian genetic model (GA) combined with energy estimation based on rigid and flexible conformation grids. In addition, molecular dynamics studies were also performed to verify the stability of the receptor-ligand complexes formed through analyses of RMSD, RMSF, H-Bond, SASA, and MMGBSA. Compared to the binding energy of the synthetic redocking coupling (-6.8 kcal/mol/RMSD of 1.34 Å), which was considerably higher, it was then decided to analyze the parameters of only three ligands: ergotamine (-9.9 kcal/mol/RMSD of 2.0 Å), dihydroergotamine (-9.8 kcal/mol/RMSD of 1.46 Å) and olysio (-9.5 kcal/mol/RMSD of 1.5 Å). It can be stated that ergotamine showed the best interactions with the M[SUP]pro[/SUP] protease of Covid-19 in the in silico study, showing itself as a promising candidate for treating Covid-19.
Keywords: Coronavirus; Ligand; Molecular docking; Receptor; Virtual screening; covid19.