| Title: | Identification of triazolopyrimidinyl scaffold SARS-CoV-2 papain-like protease (PLpro) inhibitor |
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| Authors: | ID Kralj, Sebastjan (Author)
ID Jukič, Marko (Author)
ID Bahun, Miha (Author)
ID Kranjc, Luka (Author)
ID Kolarič, Anja (Author)
ID Hodošček, Milan (Author)
ID Poklar Ulrih, Nataša (Author)
ID Bren, Urban (Author) |
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| Files: |  URL - Source URL, visit https://dk.um.si/IzpisGradiva.php?id=86901
 PDF - Presentation file, download (6,86 MB)
MD5: CA3191C422FA5AF327E58194FCEA67DE
URL - Source URL, visit https://doi.org/10.3390/pharmaceutics16020169
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  NIB - National Institute of Biology
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| Abstract: | The global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its companion disease, COVID-19, has reminded us of the importance of basic coronaviral research. In this study, a comprehensive approach using molecular docking, in vitro assays, and molecular dynamics simulations was applied to identify potential inhibitors for SARS-CoV-2 papain-like protease (PLpro), a key and underexplored viral enzyme target. A focused protease inhibitor library was initially created and molecular docking was performed using CmDock software (v0.2.0), resulting in the selection of hit compounds for in vitro testing on the isolated enzyme. Among them, compound 372 exhibited promising inhibitory properties against PLpro, with an IC50 value of 82 ± 34 μM. The compound also displayed a new triazolopyrimidinyl scaffold not yet represented within protease inhibitors. Molecular dynamics simulations demonstrated the favorable binding properties of compound 372. Structural analysis highlighted its key interactions with PLpro, and we stress its potential for further optimization. Moreover, besides compound 372 as a candidate for PLpro inhibitor development, this study elaborates on the PLpro binding site dynamics and provides a valuable contribution for further efforts in pan-coronaviral PLpro inhibitor development.
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| Keywords: | drug design, protease inhibitor, SARS-CoV-2, papain-like protease, PLpro, antiviral design, in silico drug design, CADD, virtual screening, HTVS, structure-based design |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Publication date: | 25.01.2024 |
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| Year of publishing: | 2024 |
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| Number of pages: | 13 str. |
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| Numbering: | Vol. 16, issue 2, [article no.] 169 |
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| PID: | 20.500.12556/DiRROS-20177  |
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| UDC: | 60:543.2/.9 |
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| ISSN on article: | 1999-4923 |
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| DOI: | 10.3390/pharmaceutics16020169 |
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| COBISS.SI-ID: | 182627331 |
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| Note: | Nasl. z nasl. zaslona;
Soavtorji: Marko Jukič, Miha Bahun, Luka Kranjc, Anja Kolarič, Milan Hodošček, Nataša Poklar Ulrih, Urban Bren;
Opis vira z dne 26. 1. 2024;
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| Publication date in DiRROS: | 07.08.2024 |
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| Views: | 351 |
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| Downloads: | 266 |
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