Peptide-Based Inhibitors of Protein–Protein Interactions (PPIs): A Case Study on the Interaction Between SARS-CoV-2 Spike Protein and Human Angiotensin-Converting Enzyme 2 (hACE2)
Abstract
:1. Introduction
2. Complex Structure of hACE and Spike Proteins
3. Native Peptides
4. Mutated Peptides
5. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Feature 1 | hACE2 | Spike |
---|---|---|
No. of interface residues | 19 | 17 |
Interface area | 825 | 863 |
No. of H-bonds | 11 | |
No. of salt bridges | 1 | |
No. nonbonded contacts | 106 |
hACE2: | 19 | 20 | 21 | 22 | 23 | 24 | 25 | 26 | 27 | 28 | 29 | 30 | 31 | 32 | 33 | 34 | 35 | 36 | 37 | 38 | 39 | 40 | 41 | 42 | 43 | 44 | 45 | 46 | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
First Author | Peptide Name | S | T | I | E | E | Q | A | K | T | F | L | D | K | F | N | H | E | A | E | D | L | F | Y | Q | S | S | L | A |
Larue [33] | SAP1 | ||||||||||||||||||||||||||||
SAP2 | |||||||||||||||||||||||||||||
SAP5 | |||||||||||||||||||||||||||||
SAP6 | |||||||||||||||||||||||||||||
Pei [35] | SI4α | ||||||||||||||||||||||||||||
SI5α | |||||||||||||||||||||||||||||
Abouhajar [36] | [30,31,32,33,34,35,36,37,38,39,40,41,42] | ||||||||||||||||||||||||||||
[22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44] | |||||||||||||||||||||||||||||
Chitsike [37] | Pep1 |
hACE2: | 19 | 20 | 21 | 22 | 23 | 24 | 25 | 26 | 27 | 28 | 29 | 30 | 31 | 32 | 33 | 34 | 35 | 36 | 37 | 38 | 39 | 40 | 41 | 42 | 43 | 44 | 45 | 46 | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
First Author | Peptide Name | S | T | I | E | E | Q | A | K | T | F | L | D | K | F | N | H | E | A | E | D | L | F | Y | Q | S | S | L | A | |||
Karoyan [38] | P1 | (1) | ||||||||||||||||||||||||||||||
P2 | A | L | L | L | L | L | (1) | |||||||||||||||||||||||||
P3 | A | L | L | L | L | L | A | (1) | ||||||||||||||||||||||||
P4 | (2) | A | L | L | L | L | L | A | (1) | |||||||||||||||||||||||
P5 | A | L | L | L | P | L | L | A | (1) | |||||||||||||||||||||||
P6 | A | L | L | L | L | L | L | (1) | ||||||||||||||||||||||||
P7 | A | L | Y | L | L | L | L | (1) | ||||||||||||||||||||||||
P8 | A | L | L | M | L | L | A | (1) | ||||||||||||||||||||||||
P9 | A | L | Y | M | L | L | (1) | |||||||||||||||||||||||||
P10 | A | L | Y | M | L | L | A | (1) | ||||||||||||||||||||||||
Chitsike [37] | Pep2 | (3) | ||||||||||||||||||||||||||||||
Pep3 | V | Y | R | D | ||||||||||||||||||||||||||||
Pep4 | P | E | L | L | L | L | E | |||||||||||||||||||||||||
Pep5 | P | E | L | L | CD | L | L | E | ||||||||||||||||||||||||
Chopra [41] | BP19 | (4) | I | |||||||||||||||||||||||||||||
Rajpoot [42] | 13AApi | N | F | K | ||||||||||||||||||||||||||||
Odolczyk [43] | pep1c | G | ||||||||||||||||||||||||||||||
pep1d | G | |||||||||||||||||||||||||||||||
pep1e | G | |||||||||||||||||||||||||||||||
J3 | Y | G |
Peptide Name | Modified * | Verification Method | IC50 ** | Binding Affinity (KD) ** | Ref. |
---|---|---|---|---|---|
SAP1 | LA (IC50); affinity precipitation assays (KD) | 2.39 ± 0.20 mM | 0.53 ± 0.01 mM | [33] | |
SAP2 | 3.72 ± 0.37 mM | 10.7 ± 4.2 mM | |||
SAP4 | >7.5 mM | -n/d | |||
SAP5 | >7.5 mM | n/d | |||
SI5α | ELISA | (EC50) 1.59 μM | n/d | [35] | |
[30,31,32,33,34,35,36,37,38,39,40,41,42] | SPR | 0.65 μg/mL | n/d | [36] | |
[22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44] | 2.00 μg/mL | n/d | |||
P8 | ELISA (IC50); BLI (KD) | 46 nM | 24 ± 11 nM | [38] | |
P9 | 53 nM | 0.09 ± 0.08 nM | |||
P10 | 42 nM | 0.03 ± 0.01 nM | |||
Pep1 | AlphaScreen™ assay | 80 μM | n/d | [37] | |
Pep2 | Y | 113 μM | n/d | ||
Pep3 | Y | 72 μM | n/d | ||
Pep4 | Y | 42 μM | n/d | ||
Pep5 | Y | 363 μM | n/d | ||
BP19 | Y | ELISA | 2.08 ± 0.38 μM | n/d | [41] |
13AApi | Y | ELISA | >100 μM | n/d | [42] |
pep1c | Y | ELISA (IC50); MST (KD) | n/d | 280 ± 60 nM | [27] |
pep1d | Y | 3.3 mM | 210 ± 50 nM | ||
pep1e | Y | n/d | 1900 ± 400 nM | ||
J3 | Y | ELISA (IC50); MST (KD) | n/d | ~50 nM | [43] |
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Rakhmetullina, A.; Zielenkiewicz, P.; Odolczyk, N. Peptide-Based Inhibitors of Protein–Protein Interactions (PPIs): A Case Study on the Interaction Between SARS-CoV-2 Spike Protein and Human Angiotensin-Converting Enzyme 2 (hACE2). Biomedicines 2024, 12, 2361. https://doi.org/10.3390/biomedicines12102361
Rakhmetullina A, Zielenkiewicz P, Odolczyk N. Peptide-Based Inhibitors of Protein–Protein Interactions (PPIs): A Case Study on the Interaction Between SARS-CoV-2 Spike Protein and Human Angiotensin-Converting Enzyme 2 (hACE2). Biomedicines. 2024; 12(10):2361. https://doi.org/10.3390/biomedicines12102361
Chicago/Turabian StyleRakhmetullina, Aizhan, Piotr Zielenkiewicz, and Norbert Odolczyk. 2024. "Peptide-Based Inhibitors of Protein–Protein Interactions (PPIs): A Case Study on the Interaction Between SARS-CoV-2 Spike Protein and Human Angiotensin-Converting Enzyme 2 (hACE2)" Biomedicines 12, no. 10: 2361. https://doi.org/10.3390/biomedicines12102361