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

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 th...

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Vydáno v:	Molecular biotechnology Ročník 66; číslo 8; s. 1919 - 1933
Hlavní autoři:	da Fonseca, Aluísio Marques, Caluaco, Bernardino Joaquim, Madureira, Junilson Martinho Canjanja, Cabongo, Sadrack Queque, Gaieta, Eduardo Menezes, Djata, Faustino, Colares, Regilany Paulo, Neto, Moises Maia, Fernandes, Carla Freire Celedonio, Marinho, Gabrielle Silva, dos Santos, Hélcio Silva, Marinho, Emmanuel Silva
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Springer US 01.08.2024 Springer Nature B.V
Témata:	Algorithms Antiviral Agents - chemistry Antiviral Agents - pharmacology Binding Sites Biochemistry Biological Techniques Biotechnology Cell Biology Chemistry Chemistry and Materials Science Clinical trials computer simulation Conformation Coronavirus 3C Proteases - antagonists & inhibitors Coronavirus 3C Proteases - chemistry Coronavirus 3C Proteases - metabolism Coronaviruses COVID-19 COVID-19 - virology COVID-19 Drug Treatment COVID-19 infection Drug development Drug screening Drugs energy Ergotamine genetic models Human Genetics Humans Hydrogen Bonding Ligands Molecular docking Molecular Docking Simulation Molecular dynamics Molecular Dynamics Simulation Molecular structure Original Paper Population genetics Protease Protease inhibitors Protease Inhibitors - chemistry Protease Inhibitors - metabolism Protease Inhibitors - pharmacology Protein Binding Protein Science Proteinase Proteinase inhibitors proteinases SARS-CoV-2 - drug effects SARS-CoV-2 - enzymology Severe acute respiratory syndrome coronavirus 2 Viral diseases Virtual screening Coronavirus Receptor Ligand Molecular docking covid19
ISSN:	1073-6085, 1559-0305, 1559-0305
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Shrnutí:	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 pro 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 pro protease of Covid-19 in the in silico study, showing itself as a promising candidate for treating Covid-19.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1073-6085 1559-0305 1559-0305
DOI:	10.1007/s12033-023-00831-x