Identifying the Most Potent Dual-Targeting Compound(s) against 3CLprotease and NSP15exonuclease of SARS-CoV-2 from Nigella sativa: Virtual Screening via Physicochemical Properties, Docking and Dynamic Simulation Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Compounds and Protein Structure Retrieval
2.2. Calculation of Physicochemical Properties and Prediction of Toxicity Potential
2.3. Molecular Docking
2.4. LIGPLOT+ Analysis
2.5. Molecular Dynamics Simulation Study
3. Results
3.1. Virtual Screening
3.1.1. Virtual Screening via Molecular Docking Analysis
3.1.2. Virtual Screening via Physicochemical Properties Analysis
3.1.3. Virtual Screening via Toxicity Assessment
3.2. Molecular Dynamic Simulation Study
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compounds | 3Clpro | Nsp15 | ||
---|---|---|---|---|
Binding Energy (ΔG) kcal/mol | Inhibition Constant (Ki) | Binding Energy (ΔG) kcal/mol | Inhibition Constant (Ki) | |
Trans-anethole | −4.92 | 246.75 μM | −5.16 | 166.25 μM |
α-Pinene | −5.76 | 60.23 μM | −5.36 | 118.03 μM |
β-Pinene | −5.80 | 55.60 μM | −5.45 | 100.81 μM |
Carvacrol | −5.20 | 153.32 μM | −5.50 | 92.57 μM |
Carvone | −5.42 | 107.14 μM | −5.55 | 85.02 μM |
p-Cymene | −4.80 | 300.76 μM | −5.19 | 157.67 μM |
Dithymoquinone | −8.56 | 531.10 nM | −8.31 | 803.86 nM |
Limonene | −5.19 | 157.44 μM | −5.28 | 134.92 μM |
Longifoline | −6.48 | 17.89 μM | −6.17 | 29.92 μM |
α-Thujene | −5.22 | 150.37 μM | −4.97 | 226.02 μM |
Thymohydroquinone | −5.35 | 120.74 μM | −5.90 | 47.45 μM |
Thymol | −5.19 | 157.16 μM | −5.27 | 136.00 μM |
Thymoquinone | −5.25 | 142.75 μM | −5.66 | 71.50 μM |
Lopinavir * | −7.95 | 1.48 μM | - | - |
Benzopurpurin B * | - | - | −5.87 | 50.15 μM |
Compounds | Physiochemical Parameters | |||||
---|---|---|---|---|---|---|
Molecular Weight (g/mol) | cLogP ** | Hydrogen Bond Donors | Hydrogen Bond Acceptors | Number of Rotatable Bonds | Lipinski’s Violation | |
Rule | <500 | ≤5 | <5 | <10 | ≤10 | ≤1 |
Trans-anethole | 148.20 | 2.68 | 0 | 1 | 2 | 0 |
α-Pinene | 136.23 | 2.72 | 0 | 0 | 0 | 0 |
β-Pinene | 136.23 | 2.79 | 0 | 0 | 0 | 0 |
Carvacrol | 150.22 | 2.84 | 1 | 1 | 1 | 0 |
Carvone | 150.22 | 2.65 | 0 | 1 | 1 | 0 |
p-Cymene | 134.22 | 3.19 | 0 | 0 | 1 | 0 |
Dithymoquinone | 328.40 | 2.73 | 0 | 4 | 2 | 0 |
Limonene | 136.23 | 3.36 | 0 | 0 | 1 | 0 |
Longifoline | 204.35 | 4.06 | 0 | 0 | 0 | 0 |
α-Thujene | 136.23 | 2.78 | 0 | 0 | 1 | 0 |
Thymohydroquinone | 166.21 | 2.49 | 2 | 2 | 1 | 0 |
Thymol | 150.22 | 2.84 | 1 | 1 | 1 | 0 |
Thymoquinone | 164.20 | 1.63 | 0 | 2 | 1 | 0 |
Lopinavir * | 628.81 | 4.84 | 4 | 9 | 15 | 2 |
Benzopurpurin B * | 680.76 | 4.98 | 4 | 12 | 7 | 2 |
Compounds | Toxicity Risks | |||
---|---|---|---|---|
Mutagenic | Tumorigenic | Reproductive Effect | Irritant | |
Trans-anethole | High | High | High | None |
α-Pinene | None | None | None | High |
β-Pinene | None | None | None | None |
Carvacrol | None | None | None | High |
Carvone | None | None | None | Low |
p-Cymene | None | Low | None | High |
Dithymoquinone | None | None | None | None |
Limonene | None | None | None | Low |
Longifoline | None | None | None | None |
α-Thujene | None | None | None | Low |
Thymohydroquinone | High | Low | None | None |
Thymol | High | None | High | None |
Thymoquinone | High | None | None | None |
Lopinavir * | None | None | None | High |
Benzopurpurin B * | High | High | High | High |
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Rizvi, S.M.D.; Hussain, T.; Moin, A.; Dixit, S.R.; Mandal, S.P.; Adnan, M.; Jamal, Q.M.S.; Sharma, D.C.; Alanazi, A.S.; Unissa, R. Identifying the Most Potent Dual-Targeting Compound(s) against 3CLprotease and NSP15exonuclease of SARS-CoV-2 from Nigella sativa: Virtual Screening via Physicochemical Properties, Docking and Dynamic Simulation Analysis. Processes 2021, 9, 1814. https://doi.org/10.3390/pr9101814
Rizvi SMD, Hussain T, Moin A, Dixit SR, Mandal SP, Adnan M, Jamal QMS, Sharma DC, Alanazi AS, Unissa R. Identifying the Most Potent Dual-Targeting Compound(s) against 3CLprotease and NSP15exonuclease of SARS-CoV-2 from Nigella sativa: Virtual Screening via Physicochemical Properties, Docking and Dynamic Simulation Analysis. Processes. 2021; 9(10):1814. https://doi.org/10.3390/pr9101814
Chicago/Turabian StyleRizvi, Syed Mohd Danish, Talib Hussain, Afrasim Moin, Sheshagiri R. Dixit, Subhankar P. Mandal, Mohd Adnan, Qazi Mohammad Sajid Jamal, Dinesh C. Sharma, Abulrahman Sattam Alanazi, and Rahamat Unissa. 2021. "Identifying the Most Potent Dual-Targeting Compound(s) against 3CLprotease and NSP15exonuclease of SARS-CoV-2 from Nigella sativa: Virtual Screening via Physicochemical Properties, Docking and Dynamic Simulation Analysis" Processes 9, no. 10: 1814. https://doi.org/10.3390/pr9101814
APA StyleRizvi, S. M. D., Hussain, T., Moin, A., Dixit, S. R., Mandal, S. P., Adnan, M., Jamal, Q. M. S., Sharma, D. C., Alanazi, A. S., & Unissa, R. (2021). Identifying the Most Potent Dual-Targeting Compound(s) against 3CLprotease and NSP15exonuclease of SARS-CoV-2 from Nigella sativa: Virtual Screening via Physicochemical Properties, Docking and Dynamic Simulation Analysis. Processes, 9(10), 1814. https://doi.org/10.3390/pr9101814