Inhibition of Human Coronavirus 229E by Lactoferrin-Derived Peptidomimetics
Abstract
1. Introduction
2. Materials and Methods
2.1. Peptide Synthesis
2.1.1. Synthesis of N-Methyl Peptides
2.1.2. Synthesis of Peptoids
2.1.3. Purification and Characterization
2.2. Biological Procedures
2.2.1. Cells
2.2.2. Virus
2.2.3. Virus Titration
2.2.4. MTT (3-[4,5-Dimethyl-2-thiazolyl]-2,5-diphenyl-2htetrazolium Bromide) Assay of Cell Viability
2.2.5. Antiviral Assay
2.3. Direct Binding Assay
2.3.1. Microscale Thermophoresis (MST)
2.3.2. Surface Plasmon Resonance (SPR)
2.3.3. Nanoscale Differential Scanning Fluorometry
2.4. Computational Studies
3. Results
3.1. Antiviral Assay
3.2. Biophysical Characterization of Spike-Binding Peptidomimetics
3.2.1. Peptidomimetic–Spike Interactions Determined by MST
3.2.2. Binding Affinity of Compounds to Spike Protein Determined by SPR
3.2.3. NanoDSF of Spike Protein–Peptidomimetics
3.3. Computational Studies
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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Compound | Sequence | Influenza A H1N1 Virus a,b | 229E Coronavirus | ||
---|---|---|---|---|---|
EC50 c (nM) | SI d | EC50 c (nM) | SI d | ||
1 | SLDC | 4.6 ± 0.05 × 10−3 | >5.4 × 106 | 50 ± 0.4 | >5 × 102 |
2 | SKHS | 4.8 ± 0.12 × 10−5 | >5.2 × 108 | 500 ± 2 | >5 × 101 |
3 | SK(N-Me)HS | 0.142 ± 0.002 | >1.78 × 103 | 0.031 ± 0.007 | >8 × 105 |
4 | S(N-Me)LDC | 0.085 ± 0.0004 | >2.9 × 105 | -- | -- |
5 | SNKHS e | 0.470 ± 0.002 | >5.3 × 104 | 0.0177 ± 0.002 | >14.1 × 105 |
6 | SKHNhS e | 0.500 ± 0.004 | >5 × 105 | -- | -- |
Compound | Sequence | Adsorption | Infection Cycle |
---|---|---|---|
3 | SK(N-Me)HS | EC25 a (nM) 4.3 ± 0.6 × 10−2 | EC50 b (nM) 4.3 ± 0.6 × 10−2 |
5 | SNKHS | EC50 b (nM) 2.5 ± 0.4 × 10−2 | EC50 b (nM) 2.0 ± 0.2 × 10−2 |
Compound | Sequence a | MST KD (µM) | SPR KD (µM) | ∆Tm (°C) |
---|---|---|---|---|
1 | SLDC | 4.92 ± 0.7 | >50 | −0.9 |
2 | SKHS | 5.12 ± 0.6 | 41.44 ± 0.87 | −0.7 |
3 | SK(N-Me)HS | 0.39 ± 0.05 | 0.416 ± 0.442 | 0.3 |
4 | S(N-Me)LDC | 2.6 ± 1.3 | 1.153 ± 0.182 | 0.1 |
5 | SNKHS | 3.3 ± 1.7 | 0.649 ± 0.076 | 0.9 |
6 | SKHNhS | 11 ± 0.8 | 1.507 ± 0.465 | 0.4 |
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Scala, M.C.; Marchetti, M.; Landi, M.; Fantacuzzi, M.; Superti, F.; Agamennone, M.; Campiglia, P.; Sala, M. Inhibition of Human Coronavirus 229E by Lactoferrin-Derived Peptidomimetics. Pharmaceutics 2025, 17, 1006. https://doi.org/10.3390/pharmaceutics17081006
Scala MC, Marchetti M, Landi M, Fantacuzzi M, Superti F, Agamennone M, Campiglia P, Sala M. Inhibition of Human Coronavirus 229E by Lactoferrin-Derived Peptidomimetics. Pharmaceutics. 2025; 17(8):1006. https://doi.org/10.3390/pharmaceutics17081006
Chicago/Turabian StyleScala, Maria Carmina, Magda Marchetti, Martina Landi, Marialuigia Fantacuzzi, Fabiana Superti, Mariangela Agamennone, Pietro Campiglia, and Marina Sala. 2025. "Inhibition of Human Coronavirus 229E by Lactoferrin-Derived Peptidomimetics" Pharmaceutics 17, no. 8: 1006. https://doi.org/10.3390/pharmaceutics17081006
APA StyleScala, M. C., Marchetti, M., Landi, M., Fantacuzzi, M., Superti, F., Agamennone, M., Campiglia, P., & Sala, M. (2025). Inhibition of Human Coronavirus 229E by Lactoferrin-Derived Peptidomimetics. Pharmaceutics, 17(8), 1006. https://doi.org/10.3390/pharmaceutics17081006