β-Tocotrienol and δ-Tocotrienol as Additional Inhibitors of the Main Protease of Feline Infectious Peritonitis Virus: An In Silico Analysis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Computational Tools
2.2. Computational Methods
2.2.1. Protein Structure Preparation
2.2.2. Database Preparation
2.2.3. Structure-Based Virtual Screening
2.2.4. Molecular Docking by iGEMDOCK
2.2.5. Binding Free Energy Estimation
2.2.6. In Silico ADMET Studies
2.3. Molecular Dynamics (MD) Studies
2.4. Density Functional Theory (DFT) Studies
3. Results
4. Discussion
4.1. Virtual Screening and Molecular Docking
4.2. ADMET and Molecular Dynamics (MD) Studies
4.3. Comprehensive Analysis and Future Directions
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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Complex | Total Energy (KJ/mole) | Energy VDW (KJ/mole) | Energy Hbond (KJ/mole) | Amino Acid Residue Hbonds | Amino Acid Residue VDW Interactions |
---|---|---|---|---|---|
β-tocotrienol-FIPV-3CLpro | −94.92 | −91.42 | −3.5 | PHE 111 | MET 6, GLN 8, GLU 291, ARG 294 |
δ-tocotrienol-FIPV-3CLpro | −98.23 | −86.32 | −11.9 | PHE 111, VAL 127 | GLY 122, GLN 8, PHE 111, ASN 112, GLU 291, ARG 294, VAL 299 |
Formula | C28H42O2 | C27H40O2 | Formula | C28H42O2 | C27H40O2 |
---|---|---|---|---|---|
Molecular weight | 410.63 g/mol | 396.61 g/mol | Total clearance | 0.814 log mL/min/kg | 0.847 log ml/min/kg |
Num. of heavy atoms | 30 | 29 | Renal OCT2 substrate | No | No |
Num. of aromatic heavy atoms | 6 | 6 | AMES toxicity | No | No |
Num. of rotatable bonds | 9 | 9 | Max. tolerated dose | 0.45 log mg/kg/day | 0.729 log mg/kg/day |
Num. of H-bond acceptors | 2 | 2 | hERG I Inhibitor | No | No |
Num. of H-bond donors | 1 | 1 | hERG II Inhibitor | Yes | Yes |
Molar refractivity | 132.88 | 127.2 | Oral rat acute toxicity (LD50) | 2.18 mol/kg | 1.945 mol/kg |
Log Po/w | 5.14 | 5.35 | Oral rat chronic toxicity (LOAEL) | 2.967 log mg/kg_bw/day | 2.956 log mg/kg_bw/day |
Log S | −7.57 | −7.26 | Hepatotoxicity | No | No |
GI absorption | Low | Low | Skin sensitisation | No | No |
BBB permeant | No | No | T. pyriformis toxicity | 1.127 log ug/L | 1.182 log ug/L |
P-gp substrate | Yes | Yes | Minnow toxicity | −2.5 mM | −4.247 mM |
CYP1A2 inhibitor | No | No | No | No | |
CYP2C19 inhibitor | No | No | |||
CYP2C9 inhibitor | No | No | |||
CYP2D6 inhibitor | No | No | |||
CYP3A4 inhibitor | No | Yes | |||
Log Kp (skin permeation) | −2.46 cm/s | −2.63 cm/s | |||
Lipinski | Yes, 1 violation: MLOGP > 4.15 | Yes, 1 violation: MLOGP > 4.15 | |||
Bioavailability Score | 0.55 | 0.55 |
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Vlasiou, M.C.; Nikolaou, G.; Spanoudes, K.; Mavrides, D.E. β-Tocotrienol and δ-Tocotrienol as Additional Inhibitors of the Main Protease of Feline Infectious Peritonitis Virus: An In Silico Analysis. Vet. Sci. 2024, 11, 424. https://doi.org/10.3390/vetsci11090424
Vlasiou MC, Nikolaou G, Spanoudes K, Mavrides DE. β-Tocotrienol and δ-Tocotrienol as Additional Inhibitors of the Main Protease of Feline Infectious Peritonitis Virus: An In Silico Analysis. Veterinary Sciences. 2024; 11(9):424. https://doi.org/10.3390/vetsci11090424
Chicago/Turabian StyleVlasiou, Manos C., Georgios Nikolaou, Kyriakos Spanoudes, and Daphne E. Mavrides. 2024. "β-Tocotrienol and δ-Tocotrienol as Additional Inhibitors of the Main Protease of Feline Infectious Peritonitis Virus: An In Silico Analysis" Veterinary Sciences 11, no. 9: 424. https://doi.org/10.3390/vetsci11090424