Montelukast and Telmisartan as Inhibitors of SARS-CoV-2 Omicron Variant
Abstract
:1. Introduction
2. Materials and Methods
2.1. Protein Structure
2.2. Molecular Docking
2.3. Molecular Dynamics (MD) Simulations
2.4. Principal Component Analysis (PCA)
2.5. Binding Energy Calculations
2.6. AutoQSAR Modeling
2.7. Chemicals
2.8. Vero Cell Culture
2.9. Cell Viability Assay
2.10. Antiviral Plaque Assay
2.11. Antiviral Testing Using RT-qPCR
2.12. Enzyme-Linked Immunosorbent Assay (ELISA)
2.13. Biolayer Interferometry (BLI)
3. Results
3.1. Molecular Docking
3.2. MD Simulations
3.3. PCA
3.4. Binding Energy Calculations
3.5. AutoQSAR Model
3.6. In Vitro Anti-SARS-CoV-2 Activity
3.7. ELISA
3.8. BLI
4. Discussion
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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Sr. No | Name | XP GScore (kcal/mol) | H-Bond | π-π Stacking | π-Cation | Polar | Hydrophobic | Negative Charged | Positive Charged | Glycine | Halogen Bond |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | Nilotinib | −7.159 | - | A: His34 | A: Arg393; E: Lys403 | A: His34, Thr324 | A: Phe356, Ala387; E: Tyr453, Tyr495, Val503, Tyr505 | A: Glu37, Asp38 | A: Lys353, Arg393; E: Lys403 | A: Gly354; E: Gly496, Gly502, Gly504 | - |
2 | Viroptic | −6.919 | A: Arg393; E: Gly496 | - | - | A: Asn33, His34 | E: Tyr453, Tyr495, Tyr505 | - | A: Lys353, Arg393; E: Lys403 | E: Gly496 | - |
3 | Darifenacin | −6.501 | - | A: His34 | A: His34; E: Lys403 | A: Asn33, His34; E: Ser494 | A: Ala386, Ala387, Pro389; E: Val417, Tyr495, Tyr505 | A: Glu37, Asp38; E: Asp405 | A: Lys353, Arg393; E: Lys403 | E: Gly496 | - |
4 | Olaparib | −6.41 | E: Gly496 | A: His34 | E: Lys403 | A: His34 | A: Ala386, Ala387; E: Tyr453, Tyr495, Phe497, Tyr505 | A: Glu37 | A: Lys353, Arg393; E: Lys403 | A: Gly354; E: Gly496 | - |
5 | Nebivolol | −6.368 | A: Asn33, Arg393 | A: His34 | - | A: Asn33, His34; E: Gln409 | E: Val417, Ile418, Tyr453, Tyr495, Tyr505 | A: Glu37 | A: Arg393 | E: Gly496 | - |
6 | Meclizine | −6.335 | - | A: His34 | A: His34 | A: Asn33, His34, Gln388 | A: Ala387, Pro389; E: Val417, Ile418, Tyr453, Tyr495, Tyr505 | A: Asp30, Glu37 | A: Arg393; E: Lys403 | E: Gly496 | E: Gly496 |
7 | Montelukast | −6.144 | E: Arg408, Tyr505 | - | A: Arg393 | A: Asn33, His34; E: Gln409, Gln493 | A: Ala386, Ala387; E: Val417, Ile418, Tyr453, Tyr505 | A: Glu37, Asp38; E: Asp406 | A: Lys353, Arg393; E: Lys403, Arg408 | E: Gly496 | E: Gln493 |
8 | Nelfinavir | −6.063 | A: Ala387 | A: His34 | - | A: Asn33, His34; E: Gln409 | A: Ala387, Pro389; E: Val417, Ile418, Tyr453, Tyr495, Tyr505 | A: Asp30, Glu37 | A: Arg393; E: Lys403 | E: Gly496 | - |
9 | Telmisartan | −5.961 | E: Tyr505 | E: Tyr505 | E: Lys403 | A: His34; E: Gln409, Gln493 | A: Phe356, Ala386, Ala387; E: Val417, Tyr453, Tyr495, Tyr505 | A: Glu37, Asp350; E: Asp405, Asp406 | A: Arg393; E: Lys403 | A: Gly352, Gly354; E: Gly496 | - |
10 | Lifitegrast | −5.701 | A: Ala386, Arg393 | - | - | A: Asn33, His34, Gln388 | A: Ala386, Ala387; E: Tyr495, Tyr505 | A: Glu37, Asp38 | A: Lys353, Arg393; E: Lys403 | E: Gly496 | - |
Name | ΔGCoulomb | ΔGCovalent | ΔGLipophilic | ΔGvdW | ΔGGB solv | ΔGBind | ΔEStrain |
---|---|---|---|---|---|---|---|
Nilotinib | −12.33 ± 4.06 | 4.33 ± 2.57 | −17.07 ± 1.75 | −54.51 ± 5.00 | 33.82 ± 3.42 | −50.57 ± 6.12 | 3.77 ± 1.80 |
Viroptic | −18.27 ± 3.12 | 2.66 ± 1.12 | −6.52 ± 0.45 | −32.27 ± 1.29 | 21.72 ± 2.11 | −34.51 ± 3.24 | 2.63 ± 0.97 |
Darifenacin | −20.25 ± 9.51 | 1.85 ± 0.78 | −16.28 ± 5.43 | −44.29 ± 5.44 | 29.64 ± 10.96 | −52.05 ± 9.26 | 5.71 ± 5.66 |
Olaparib | −6.36 ± 3.80 | 3.28 ± 2.02 | −15.91 ± 1.92 | −49.06 ± 2.97 | 27.87 ± 2.99 | −43.15 ± 5.12 | 3.94 ± 1.46 |
Nebivolol | −22.29 ± 7.77 | 2.78 ± 0.99 | −18.50 ± 1.41 | −44.49 ± 2.03 | 36.69 ± 7.60 | −48.48 ± 6.18 | 2.86 ± 1.37 |
Meclizine | −29.68 ± 7.63 | 2.09 ± 0.96 | −22.14 ± 1.73 | −43.05 ± 2.82 | 47.27 ± 5.78 | −48.57 ± 4.47 | 2.51 ± 0.84 |
Montelukast | 20.92 ± 13.07 | 2.92 ± 0.73 | −21.38 ± 1.22 | −63.13 ± 2.17 | 6.61 ± 12.47 | −61.40 ± 3.85 | 8.51 ± 2.13 |
Nelfinavir | −29.11 ± 8.49 | 1.86 ± 3.19 | −17.28 ± 5.00 | −49.58 ± 4.65 | 44.57 ± 6.65 | −53.16 ± 12.01 | 6.78 ± 3.77 |
Telmisartan | 41.34 ± 11.97 | 4.66 ± 1.88 | −20.18 ± 1.03 | −65.95 ± 2.44 | −20.26 ± 9.41 | −67.69 ± 5.51 | 3.26 ± 0.70 |
Lifitegrast | −32.99 ± 11.30 | 1.89 ± 0.99 | −16.16 ± 2.38 | −39.30 ± 3.24 | 38.70 ± 9.67 | −50.18 ± 7.75 | 3.22 ± 1.48 |
Name | Binding Affinity (kcal/mol) | Predicted Affinity (kcal/mol) | RMSE (kcal/mol) |
---|---|---|---|
Nilotinib | −7.159 | −4.876 | 2.283 |
Viroptic | −6.919 | −3.892 | 3.027 |
Darifenacin | −6.501 | −3.445 | 3.056 |
Olaparib | −6.41 | −4.087 | 2.323 |
Nebivolol | −6.368 | −5.435 | 0.933 |
Meclizine | −6.335 | −3.861 | 2.474 |
Montelukast | −6.144 | −4.266 | 1.878 |
Nelfinavir | −6.063 | −4.759 | 1.304 |
Telmisartan | −5.961 | −4.599 | 1.362 |
Lifitegrast | −5.701 | −5.363 | 0.338 |
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Mulgaonkar, N.; Wang, H.; Zhang, J.; Roundy, C.M.; Tang, W.; Chaki, S.P.; Pauvolid-Corrêa, A.; Hamer, G.L.; Fernando, S. Montelukast and Telmisartan as Inhibitors of SARS-CoV-2 Omicron Variant. Pharmaceutics 2023, 15, 1891. https://doi.org/10.3390/pharmaceutics15071891
Mulgaonkar N, Wang H, Zhang J, Roundy CM, Tang W, Chaki SP, Pauvolid-Corrêa A, Hamer GL, Fernando S. Montelukast and Telmisartan as Inhibitors of SARS-CoV-2 Omicron Variant. Pharmaceutics. 2023; 15(7):1891. https://doi.org/10.3390/pharmaceutics15071891
Chicago/Turabian StyleMulgaonkar, Nirmitee, Haoqi Wang, Junrui Zhang, Christopher M. Roundy, Wendy Tang, Sankar Prasad Chaki, Alex Pauvolid-Corrêa, Gabriel L. Hamer, and Sandun Fernando. 2023. "Montelukast and Telmisartan as Inhibitors of SARS-CoV-2 Omicron Variant" Pharmaceutics 15, no. 7: 1891. https://doi.org/10.3390/pharmaceutics15071891