Is PF-00835231 a Pan-SARS-CoV-2 Mpro Inhibitor? A Comparative Study
Abstract
:1. Introduction
2. Result and Discussion
3. Materials and Methods
3.1. Protein Structure Preparation
3.2. Ligand Structure Preparation
3.3. Redocking: Co-Crystallized Ligand Pose Validation Study
3.4. Virtual Screening
3.5. Molecular Dynamics Simulation
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Protein | Inhibitor | Score | Residues | |
---|---|---|---|---|
Hydrogen Bond | Pi Interactions | |||
WT | PF-00835231 | 83.13 | G143, C145, H164, E166, Q189 | H41, P168 |
Manidipine | 72.93 | F140, N142, E166 | H41, L141, M165 | |
Boceprevir | 67.42 | N142, E166, Q189 | H41, M49, C145 | |
Lercanidipine | 69.73 | Q189, Q192 | C145, M165, L167, P168 | |
Efonidipine | 71.23 | H41, C145, M165, P168, A191 | ||
Bedaquiline | 66.92 | N142 | H41 |
Protein | Inhibitor | Score | Residues | |
---|---|---|---|---|
Hydrogen Bond | Pi Interactions | |||
Mutant 1 (Y54C) | PF-00835231 | 73.17 | L141, G143, S144, C145, E166, Q189 | M49, P168 |
Manidipine | 66.68 | T26, S46 | C145, M165 | |
Boceprevir | 65.96 | T26, G143, C145, E166, Q189 | H41, M49, H163, M165 | |
Lercanidipine | 65.28 | T26, G143, C145 | L27, H41, M165 | |
Efonidipine | 68.23 | L141, G143, S144, Q189 | L27, C145, H163, P168, H172 | |
Bedaquiline | 63.27 | H164 | L27, H41, M49, C145 |
Protein | Inhibitor | Score | Residues | |
---|---|---|---|---|
Hydrogen Bond | Pi Interaction | |||
Mutant 2 N142S | PF-00835231 | 76.53 | L141, S142, G143, E166, Q189 | S144, C145, L167, P168 |
Manidipine | 68.64 | F140, E166 | L141, M165 | |
Boceprevir | 65.33 | Q189 | C44, M49, C145, H163, M165 | |
Lercanidipine | 69.05 | L27, M49, C145, H163 | ||
Efonidipine | 87.05 | S142, C145 | L27, M49, M165, L167 | |
Bedaquiline | 68.83 | H164 | H41, M49, C145, M165 |
Protein | Inhibitor | Score | Residues | |
---|---|---|---|---|
Hydrogen Bond | Pi Interactions | |||
Mutant 3 T190I | PF-00835231 | 70.66 | E166, D187, Q189 | C44, M49, C145, H163, M165 |
Manidipine | 63.42 | F140, N142 | M49, L141, M165 | |
Boceprevir | 60.36 | N142 | C44, T45, M165 | |
Lercanidipine | 66.96 | T26 | L27, H41, C44, M49, C145, M165 | |
Efonidipine | 72.25 | F140, E166 | L141, H163, M165, H172 | |
Bedaquiline | 67.87 | E166 | H41, C145 |
Protein | Inhibitor | Score | Residues | |
---|---|---|---|---|
Hydrogen Bond | Pi Interaction | |||
Mutant 4 A191V | PF-00835231 | 73.61 | L141, G143, S144, C145, Q189 | M165, P168, H172, V191 |
Manidipine | 65.95 | T25, S46, N142 | M165 | |
Boceprevir | 62.08 | S46, Q189 | C44, M49, M165 | |
Lercanidipine | 67.93 | C44, S46, N142 | H41, M49, C145, M165 | |
Efonidipine | 71.01 | F140 | L141, H163, M165, P168 | |
Bedaquiline | 59.99 | N142 | H41, C145, M165 |
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Baig, M.H.; Sharma, T.; Ahmad, I.; Abohashrh, M.; Alam, M.M.; Dong, J.-J. Is PF-00835231 a Pan-SARS-CoV-2 Mpro Inhibitor? A Comparative Study. Molecules 2021, 26, 1678. https://doi.org/10.3390/molecules26061678
Baig MH, Sharma T, Ahmad I, Abohashrh M, Alam MM, Dong J-J. Is PF-00835231 a Pan-SARS-CoV-2 Mpro Inhibitor? A Comparative Study. Molecules. 2021; 26(6):1678. https://doi.org/10.3390/molecules26061678
Chicago/Turabian StyleBaig, Mohammad Hassan, Tanuj Sharma, Irfan Ahmad, Mohammed Abohashrh, Mohammad Mahtab Alam, and Jae-June Dong. 2021. "Is PF-00835231 a Pan-SARS-CoV-2 Mpro Inhibitor? A Comparative Study" Molecules 26, no. 6: 1678. https://doi.org/10.3390/molecules26061678