SARS-CoV-2 papain-like protease (PLpro) inhibitory and antiviral activity of small molecule derivatives for drug leads
Copyright © 2023 Elsevier Ltd. All rights reserved..
We report here the synthesis and biological evaluation of a series of small molecule SARS-CoV-2 PLpro inhibitors. We compared the activity of selected compounds in both SARS-CoV-1 and SARS-CoV-2 PLpro inhibitory and antiviral assays. We have synthesized and evaluated several new structural variants of previous leads against SARS-CoV-2 PLpro. The replacement of the carboxamide functionality with sulfonamide derivatives resulted in PLpro inhibitors with potent PLpro inhibitory and antiviral activity in VeroE6 cells similar to GRL0617. To obtain molecular insight, we created an optimized model of a potent sulfonamide derivative in the SARS-CoV-2 PLpro active site.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:96 |
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| Enthalten in: |
Bioorganic & medicinal chemistry letters - 96(2023) vom: 15. Nov., Seite 129489 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ghosh, Arun K [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.11.2023 Date Revised 07.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bmcl.2023.129489 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2023 Elsevier Ltd. All rights reserved. | ||
| 520 | |a We report here the synthesis and biological evaluation of a series of small molecule SARS-CoV-2 PLpro inhibitors. We compared the activity of selected compounds in both SARS-CoV-1 and SARS-CoV-2 PLpro inhibitory and antiviral assays. We have synthesized and evaluated several new structural variants of previous leads against SARS-CoV-2 PLpro. The replacement of the carboxamide functionality with sulfonamide derivatives resulted in PLpro inhibitors with potent PLpro inhibitory and antiviral activity in VeroE6 cells similar to GRL0617. To obtain molecular insight, we created an optimized model of a potent sulfonamide derivative in the SARS-CoV-2 PLpro active site | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Antiviral | |
| 650 | 4 | |a Covid-19 | |
| 650 | 4 | |a Inhibitor | |
| 650 | 4 | |a SARS-CoV-2 protease | |
| 650 | 4 | |a Synthesis | |
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| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Sulfonamides |2 NLM | |
| 700 | 1 | |a Shahabi, Dana |e verfasserin |4 aut | |
| 700 | 1 | |a Imhoff, Mackenzie E C |e verfasserin |4 aut | |
| 700 | 1 | |a Kovela, Satish |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Ashish |e verfasserin |4 aut | |
| 700 | 1 | |a Hattori, Shin-Ichiro |e verfasserin |4 aut | |
| 700 | 1 | |a Higashi-Kuwata, Nobuyo |e verfasserin |4 aut | |
| 700 | 1 | |a Mitsuya, Hiroaki |e verfasserin |4 aut | |
| 700 | 1 | |a Mesecar, Andrew D |e verfasserin |4 aut | |
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