Article ; Online: Identification of natural inhibitors against Mpro of SARS-CoV-2 by molecular docking, molecular dynamics simulation, and MM/PBSA methods.
Journal of biomolecular structure & dynamics
2020 Volume 40, Issue 6, Page(s) 2757–2768
Abstract: ... a stable complex with Mpro and could be used as potential inhibitors of SARS-CoV-2 Mpro. However, further ... against COVID-19. The main protease (Mpro) of SARS-CoV-2 is a critical drug target as it plays ... analysis, and MM/PBSA calculations. The results of 100 ns MD simulation, RMSF, SASA, Rg, and MM/PBSA show ...
| Abstract | The recent outbreak of SARS-CoV-2 disease, also known as COVID-19, has emerged as a pandemic. The unavailability of specific therapeutic drugs and vaccines urgently demands sincere efforts for drug discovery against COVID-19. The main protease (Mpro) of SARS-CoV-2 is a critical drug target as it plays an essential role in virus replication. Therefore for the identification of potential inhibitors of SARS-CoV-2 Mpro, we applied a structure-based virtual screening approach followed by molecular dynamics (MD) study. A library of 686 phytochemicals was subjected to virtual screening which resulted in 28 phytochemicals based on binding energy. These phytochemicals were further subjected to drug-likeness and toxicity analysis, which resulted in seven drug-like hits. Out of seven, five phytochemicals viz., Mpro-Dehydrtectol (-10.3 kcal/mol), Epsilon-viniferin (-8.6 kcal/mol), Peimisine (-8.6 kcal/mol), Gmelanone (-8.4 kcal/mol), and Isocolumbin (-8.4 kcal/mol) were non-toxic. Consequently, these phytochemicals are subjected to MD, post MD analysis, and MM/PBSA calculations. The results of 100 ns MD simulation, RMSF, SASA, Rg, and MM/PBSA show that Epsilon-viniferin (-29.240 kJ/mol), Mpro-Peimisine (-43.031 kJ/mol) and Gmelanone (-13.093 kJ/mol) form a stable complex with Mpro and could be used as potential inhibitors of SARS-CoV-2 Mpro. However, further investigation of these inhibitors against Mpro receptor of COVID-19 is needed to validate their candidacy for clinical trials. Communicated by Ramaswamy H. Sarma. |
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| MeSH term(s) | Humans ; COVID-19 Drug Treatment ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Peptide Hydrolases/metabolism ; Protease Inhibitors/chemistry ; Protease Inhibitors/pharmacology ; SARS-CoV-2 |
| Chemical Substances | Peptide Hydrolases (EC 3.4.-) ; Protease Inhibitors |
| Keywords | covid19 |
| Language | English |
| Publishing date | 2020-11-04 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 49157-3 |
| ISSN | 1538-0254 ; 0739-1102 |
| ISSN (online) | 1538-0254 |
| ISSN | 0739-1102 |
| DOI | 10.1080/07391102.2020.1842806 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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