Scaffold Hopping of α-Rubromycin Enables Direct Access to FDA-Approved Cromoglicic Acid as a SARS-CoV-2 MPro Inhibitor
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Isolation of α-Rubromycin
4.2. In-Vitro Assays
4.2.1. MPro Inhibition
4.2.2. MTT Cytotoxicity Assay
4.3. In Silico Investigation
4.3.1. Ensemble Docking
4.3.2. Molecular Dynamics Simulation
4.3.3. Binding Free Energy Calculations
4.3.4. Drug-Likeness Analysis
4.3.5. Toxicity Prediction
4.3.6. Pharmacophore-Based Screening
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound | Docking SCORE | ΔG * | Interactions | ||
---|---|---|---|---|---|
H-Bonding | Water Bridges | Hydrophobic | |||
α-Rubromycin | −8.2 kcal/mol | −8.8 kcal/mol | THR-24, THR-25, HIS-41, ASN-142, GLU-166, GLN-189 | ARG-188 | MET-49, CYS-145, MET-165 |
ScafA | −8.2 kcal/mol | −8.9 kcal/mol | THR-24, THR-25, HIS-41 **, ASN-142, GLU-166, GLN-189 | GLU-166, ASN-142, ARG-188 | MET-49, CYS-145, MET-165 |
Cromoglicic acid | −8.3 kcal/mol | −9.2 kcal/mol | THR-24, THR-25, HIS-41 **, SER-46, ASN-142, GLY-143, GLN-189 | HIS-164, ARG-188 | MET-49, CYS-145, MET-165 |
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Alhadrami, H.A.; Sayed, A.M.; Al-Khatabi, H.; Alhakamy, N.A.; Rateb, M.E. Scaffold Hopping of α-Rubromycin Enables Direct Access to FDA-Approved Cromoglicic Acid as a SARS-CoV-2 MPro Inhibitor. Pharmaceuticals 2021, 14, 541. https://doi.org/10.3390/ph14060541
Alhadrami HA, Sayed AM, Al-Khatabi H, Alhakamy NA, Rateb ME. Scaffold Hopping of α-Rubromycin Enables Direct Access to FDA-Approved Cromoglicic Acid as a SARS-CoV-2 MPro Inhibitor. Pharmaceuticals. 2021; 14(6):541. https://doi.org/10.3390/ph14060541
Chicago/Turabian StyleAlhadrami, Hani A., Ahmed M. Sayed, Heba Al-Khatabi, Nabil A. Alhakamy, and Mostafa E. Rateb. 2021. "Scaffold Hopping of α-Rubromycin Enables Direct Access to FDA-Approved Cromoglicic Acid as a SARS-CoV-2 MPro Inhibitor" Pharmaceuticals 14, no. 6: 541. https://doi.org/10.3390/ph14060541
APA StyleAlhadrami, H. A., Sayed, A. M., Al-Khatabi, H., Alhakamy, N. A., & Rateb, M. E. (2021). Scaffold Hopping of α-Rubromycin Enables Direct Access to FDA-Approved Cromoglicic Acid as a SARS-CoV-2 MPro Inhibitor. Pharmaceuticals, 14(6), 541. https://doi.org/10.3390/ph14060541