Computer Aided Structure-Based Drug Design of Novel SARS-CoV-2 Main Protease Inhibitors: Molecular Docking and Molecular Dynamics Study Full article
| Journal |
Computation
ISSN: 2079-3197 |
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| Output data | Year: 2024, Volume: 12, Number: 1, Article number : 18, Pages count : 21 DOI: 10.3390/computation12010018 | ||||||
| Tags | gromacs; structure-based drug design; SBDD; SARS-CoV-2; Mpro | ||||||
| Authors |
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| Affiliations |
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Funding (2)
| 1 | Ministry of Science and Higher Education of the Russian Federation | 075-15-2021-1355 (121120100401-9) |
| 2 | Ministry of Science and Higher Education of the Russian Federation | FWUR-2024-0040 |
Abstract:
Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) virus syndrome caused the recent outbreak of COVID-19 disease, the most significant challenge to public health for decades. Despite the successful development of vaccines and promising therapies, the development of novel drugs is still in the interests of scientific society. SARS-CoV-2 main protease Mpro is one of the key proteins for the lifecycle of the virus and is considered an intriguing target. We used a structure-based drug design approach as a part of the search of new inhibitors for SARS-CoV-2 Mpro and hence new potential drugs for treating COVID-19. Four structures of potential inhibitors of (4S)-2-(2-(1H-imidazol-5-yl)ethyl)-4-amino-2-(1,3-dihydroxypropyl)-3-hydroxy-5-(1H-imidazol-5-yl)pentanal (L1), (2R,4S)-2-((1H-imidazol-4-yl)methyl)-4-chloro-8-hydroxy-7-(hydroxymethyl)octanoic acid (L2), 1,9-dihydroxy-6-(hydroxymethyl)-6-(((1S)-1,7,7-trimethylbicyclo [2.2.1]heptan-2-yl)amino)nonan-4-one (L3), and 2,4,6-tris((4H-1,2,4-triazol-3-yl)amino)benzonitrile (L4) were modeled. Three-dimensional structures of ligand–protein complexes were modeled and their potential binding efficiency proved. Docking and molecular dynamic simulations were performed for these compounds. Detailed trajectory analysis of the ligands’ binding conformation was carried out. Binding free energies were estimated by the MM/PBSA approach. Results suggest a high potential efficiency of the studied inhibitors.
Cite:
Kolybalov D.S.
, Kadtsyn E.D.
, Arkhipov S.G.
Computer Aided Structure-Based Drug Design of Novel SARS-CoV-2 Main Protease Inhibitors: Molecular Docking and Molecular Dynamics Study
Computation. 2024. V.12. N1. 18 :1-21. DOI: 10.3390/computation12010018 WOS Scopus AN OpenAlex publication_identifier_short.sciact_skif_identifier_type
Computer Aided Structure-Based Drug Design of Novel SARS-CoV-2 Main Protease Inhibitors: Molecular Docking and Molecular Dynamics Study
Computation. 2024. V.12. N1. 18 :1-21. DOI: 10.3390/computation12010018 WOS Scopus AN OpenAlex publication_identifier_short.sciact_skif_identifier_type
Dates:
| Submitted: | Oct 11, 2023 |
| Accepted: | Jan 16, 2024 |
| Published print: | Jan 20, 2024 |
| Published online: | Jan 20, 2024 |
Identifiers:
| Web of science: | WOS:001151832700001 |
| Scopus: | 2-s2.0-85183093841 |
| Chemical Abstracts: | 2024:294987 |
| OpenAlex: | W4391104899 |
| publication_identifier.sciact_skif_identifier_type: | 1069 |