Potential Novel Thioether-Amide or Guanidine-Linker Class of SARS-CoV-2 Virus RNA-Dependent RNA Polymerase Inhibitors Identified by High-Throughput Virtual Screening Coupled to Free-Energy Calculations
Abstract
:1. Introduction
2. Database Preparation
3. Molecular Dynamics and Clustering
4. Target Preparation
5. Virtual Screening
6. Free-Energy Calculations
7. Results and Discussion
8. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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No. | Structure | Mr (g/mol) | Smiles | Cluster | Ensemble Docking Score |
---|---|---|---|---|---|
1 | 336.4 | CC(NC(NC(Nc(cc1)ccc1Oc1ccccc1)=[NH2+])=N1)=CC1=O | 13 | −12.72 | |
2 | 311.4 | CC(N=C(NC(NCCc1c[nH]c2c1cccc2)=[NH2+])N1)=CC1=O | 11 | −12.68 | |
3 | 328.4 | CCOc(cc1)ccc1NC(NC(NC1=C2CCCC1)=NC2=O)=[NH2+] | 15 | −12.23 | |
4 | 266.3 | Nc1n[nH]c(SCC(NC(c2ccc[nH]2)=O)=O)n1 | 2 | −11.59 | |
5 | 380.5 | Cc(cc1)ccc1NC(NC(NC(CSc1ccc(C)cc1)=C1)=NC1=O)=[NH2+] | 14 | −11.51 | |
6 * | GS-441524 (remdesivir metabolite) | 291.3 | C1(C(N)=N2)N(N=C2)C(=CC=1)[C@@](O1)(C#N)[C@@H]([C@H](O)[C@H]1CO)O | / | −10.96 |
7 * | favipiravir-ribose | 289.2 | [C@@H]1(N(C=C2F)C(=O)C(=N2)C(=O)N)O[C@H](CO)([C@@H](O)[C@H]1O) | / | −10.78 |
8 * | GS-461203 (sofosbuvir metabolite) | 260.2 | C1=CC(NC(=O)N1[C@H](O[C@H]1CO)[C@](C)(F)[C@@H]1O)=O | / | −10.24 |
Compound | Free VdW (Kcal/Mol) | Free Coulomb (Kcal/Mol) | Complex VdW Weighted Sum (Kcal/Mol) | Complex Coulomb Weighted Sum (Kcal/Mol) | |
---|---|---|---|---|---|
1 | −6.0 ± 0.1 | −19.8 ± 0.2 | −9.3 ± 0.5 | −19.1 ± 0.6 | −2.6 ± 0.6 |
4 | −3.4 ± 0.1 | −46.0 ± 0.8 | −6.6 ± 0.1 | −49.4 ± 0.8 | −6.5 ± 0.8 |
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Jukič, M.; Janežič, D.; Bren, U. Potential Novel Thioether-Amide or Guanidine-Linker Class of SARS-CoV-2 Virus RNA-Dependent RNA Polymerase Inhibitors Identified by High-Throughput Virtual Screening Coupled to Free-Energy Calculations. Int. J. Mol. Sci. 2021, 22, 11143. https://doi.org/10.3390/ijms222011143
Jukič M, Janežič D, Bren U. Potential Novel Thioether-Amide or Guanidine-Linker Class of SARS-CoV-2 Virus RNA-Dependent RNA Polymerase Inhibitors Identified by High-Throughput Virtual Screening Coupled to Free-Energy Calculations. International Journal of Molecular Sciences. 2021; 22(20):11143. https://doi.org/10.3390/ijms222011143
Chicago/Turabian StyleJukič, Marko, Dušanka Janežič, and Urban Bren. 2021. "Potential Novel Thioether-Amide or Guanidine-Linker Class of SARS-CoV-2 Virus RNA-Dependent RNA Polymerase Inhibitors Identified by High-Throughput Virtual Screening Coupled to Free-Energy Calculations" International Journal of Molecular Sciences 22, no. 20: 11143. https://doi.org/10.3390/ijms222011143