Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases
Copyright © 2022 Elsevier B.V. All rights reserved..
Despite the fast development of vaccines, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still circulates through variants of concern (VoC) and escape the humoral immune response. SARS-CoV-2 has provoked over 200,000 deaths/months since its emergence and only a few antiviral drugs showed clinical benefit up to this moment. Thus, chemical structures endowed with anti-SARS-CoV-2 activity are important for continuous antiviral development and natural products represent a fruitful source of substances with biological activity. In the present study, agathisflavone (AGT), a biflavonoid from Anacardium occidentale was investigated as a candidate anti-SARS-CoV-2 compound. In silico and enzymatic analysis indicated that AGT may target mainly the viral main protease (Mpro) and not the papain-like protease (PLpro) in a non-competitive way. Cell-based assays in type II pneumocytes cell lineage (Calu-3) showed that SARS-CoV-2 is more susceptible to AGT than to apigenin (APG, monomer of AGT), in a dose-dependent manner, with an EC50 of 4.23 ± 0.21 μM and CC50 of 61.3 ± 0.1 μM and with a capacity to inhibit the level of pro-inflammatory mediator tumor necrosis factor-alpha (TNF-α). These results configure AGT as an interesting chemical scaffold for the development of novel semisynthetic antivirals against SARS-CoV-2.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:222 |
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| Enthalten in: |
International journal of biological macromolecules - 222(2022), Pt A vom: 01. Dez., Seite 1015-1026 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chaves, Otávio Augusto [VerfasserIn] |
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| Links: |
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| Themen: |
28441-98-7 |
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| Anmerkungen: |
Date Completed 09.11.2022 Date Revised 17.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijbiomac.2022.09.204 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM346992516 |
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| 520 | |a Despite the fast development of vaccines, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still circulates through variants of concern (VoC) and escape the humoral immune response. SARS-CoV-2 has provoked over 200,000 deaths/months since its emergence and only a few antiviral drugs showed clinical benefit up to this moment. Thus, chemical structures endowed with anti-SARS-CoV-2 activity are important for continuous antiviral development and natural products represent a fruitful source of substances with biological activity. In the present study, agathisflavone (AGT), a biflavonoid from Anacardium occidentale was investigated as a candidate anti-SARS-CoV-2 compound. In silico and enzymatic analysis indicated that AGT may target mainly the viral main protease (Mpro) and not the papain-like protease (PLpro) in a non-competitive way. Cell-based assays in type II pneumocytes cell lineage (Calu-3) showed that SARS-CoV-2 is more susceptible to AGT than to apigenin (APG, monomer of AGT), in a dose-dependent manner, with an EC50 of 4.23 ± 0.21 μM and CC50 of 61.3 ± 0.1 μM and with a capacity to inhibit the level of pro-inflammatory mediator tumor necrosis factor-alpha (TNF-α). These results configure AGT as an interesting chemical scaffold for the development of novel semisynthetic antivirals against SARS-CoV-2 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Fintelman-Rodrigues, Natalia |e verfasserin |4 aut | |
| 700 | 1 | |a Sacramento, Carolina Q |e verfasserin |4 aut | |
| 700 | 1 | |a de Freitas, Caroline S |e verfasserin |4 aut | |
| 700 | 1 | |a Vazquez, Leonardo |e verfasserin |4 aut | |
| 700 | 1 | |a Temerozo, Jairo R |e verfasserin |4 aut | |
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| 700 | 1 | |a Castro-Faria-Neto, Hugo Caire |e verfasserin |4 aut | |
| 700 | 1 | |a Souza, Thiago Moreno L |e verfasserin |4 aut | |
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