Non-Toxic Dimeric Peptides Derived from the Bothropstoxin-I Are Potent SARS-CoV-2 and Papain-like Protease Inhibitors
The COVID-19 outbreak has rapidly spread on a global scale, affecting the economy and public health systems throughout the world. In recent years, peptide-based therapeutics have been widely studied and developed to treat infectious diseases, including viral infections. Herein, the antiviral effects of the lysine linked dimer des-Cys11, Lys12,Lys13-(pBthTX-I)2K ((pBthTX-I)2K)) and derivatives against SARS-CoV-2 are reported. The lead peptide (pBthTX-I)2K and derivatives showed attractive inhibitory activities against SARS-CoV-2 (EC50 = 28-65 µM) and mostly low cytotoxic effect (CC50 > 100 µM). To shed light on the mechanism of action underlying the peptides' antiviral activity, the Main Protease (Mpro) and Papain-Like protease (PLpro) inhibitory activities of the peptides were assessed. The synthetic peptides showed PLpro inhibition potencies (IC50s = 1.0-3.5 µM) and binding affinities (Kd = 0.9-7 µM) at the low micromolar range but poor inhibitory activity against Mpro (IC50 > 10 µM). The modeled binding mode of a representative peptide of the series indicated that the compound blocked the entry of the PLpro substrate toward the protease catalytic cleft. Our findings indicated that non-toxic dimeric peptides derived from the Bothropstoxin-I have attractive cellular and enzymatic inhibitory activities, thereby suggesting that they are promising prototypes for the discovery and development of new drugs against SARS-CoV-2 infection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Molecules (Basel, Switzerland) - 26(2021), 16 vom: 12. Aug. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Freire, Marjorie C L C [VerfasserIn] |
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| Links: |
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| Themen: |
116189-59-4 |
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| Anmerkungen: |
Date Completed 02.09.2021 Date Revised 02.09.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/molecules26164896 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM329863916 |
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| 245 | 1 | 0 | |a Non-Toxic Dimeric Peptides Derived from the Bothropstoxin-I Are Potent SARS-CoV-2 and Papain-like Protease Inhibitors |
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| 500 | |a Date Completed 02.09.2021 | ||
| 500 | |a Date Revised 02.09.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The COVID-19 outbreak has rapidly spread on a global scale, affecting the economy and public health systems throughout the world. In recent years, peptide-based therapeutics have been widely studied and developed to treat infectious diseases, including viral infections. Herein, the antiviral effects of the lysine linked dimer des-Cys11, Lys12,Lys13-(pBthTX-I)2K ((pBthTX-I)2K)) and derivatives against SARS-CoV-2 are reported. The lead peptide (pBthTX-I)2K and derivatives showed attractive inhibitory activities against SARS-CoV-2 (EC50 = 28-65 µM) and mostly low cytotoxic effect (CC50 > 100 µM). To shed light on the mechanism of action underlying the peptides' antiviral activity, the Main Protease (Mpro) and Papain-Like protease (PLpro) inhibitory activities of the peptides were assessed. The synthetic peptides showed PLpro inhibition potencies (IC50s = 1.0-3.5 µM) and binding affinities (Kd = 0.9-7 µM) at the low micromolar range but poor inhibitory activity against Mpro (IC50 > 10 µM). The modeled binding mode of a representative peptide of the series indicated that the compound blocked the entry of the PLpro substrate toward the protease catalytic cleft. Our findings indicated that non-toxic dimeric peptides derived from the Bothropstoxin-I have attractive cellular and enzymatic inhibitory activities, thereby suggesting that they are promising prototypes for the discovery and development of new drugs against SARS-CoV-2 infection | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Noske, Gabriela D |e verfasserin |4 aut | |
| 700 | 1 | |a Bitencourt, Natália V |e verfasserin |4 aut | |
| 700 | 1 | |a Sanches, Paulo R S |e verfasserin |4 aut | |
| 700 | 1 | |a Santos-Filho, Norival A |e verfasserin |4 aut | |
| 700 | 1 | |a Gawriljuk, Victor O |e verfasserin |4 aut | |
| 700 | 1 | |a de Souza, Eduardo P |e verfasserin |4 aut | |
| 700 | 1 | |a Nogueira, Victor H R |e verfasserin |4 aut | |
| 700 | 1 | |a de Godoy, Mariana O |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamura, Aline M |e verfasserin |4 aut | |
| 700 | 1 | |a Fernandes, Rafaela S |e verfasserin |4 aut | |
| 700 | 1 | |a Godoy, Andre S |e verfasserin |4 aut | |
| 700 | 1 | |a Juliano, Maria A |e verfasserin |4 aut | |
| 700 | 1 | |a Peres, Bianca M |e verfasserin |4 aut | |
| 700 | 1 | |a Barbosa, Cecília G |e verfasserin |4 aut | |
| 700 | 1 | |a Moraes, Carolina B |e verfasserin |4 aut | |
| 700 | 1 | |a Freitas-Junior, Lucio H G |e verfasserin |4 aut | |
| 700 | 1 | |a Cilli, Eduardo M |e verfasserin |4 aut | |
| 700 | 1 | |a Guido, Rafael V C |e verfasserin |4 aut | |
| 700 | 1 | |a Oliva, Glaucius |e verfasserin |4 aut | |
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