| Title: | Commercial SARS-CoV-2 targeted, protease inhibitor focused and protein–protein interaction inhibitor focused molecular libraries for virtual screening and drug design |
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| Authors: | ID Kralj, Sebastjan (Author)
ID Jukič, Marko (Author)
ID Bren, Urban (Author) |
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| Files: |  ijms-23-00393.pdf (6,53 MB)
MD5: E8B2EFB155CEA0F69918D87FB880CB9D
 https://www.mdpi.com/1422-0067/23/1/393
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| Language: | English |
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| Work type: | Article |
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| Typology: | 1.02 - Review Article |
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| Organization: | FKKT - Faculty of Chemistry and Chemical Engineering
FNM - Faculty of Natural Sciences and Mathematics
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| Abstract: | Since December 2019, the new SARS-CoV-2-related COVID-19 disease has caused a global
pandemic and shut down the public life worldwide. Several proteins have emerged as potential
therapeutic targets for drug development, and we sought out to review the commercially available
and marketed SARS-CoV-2-targeted libraries ready for high-throughput virtual screening (HTVS).
We evaluated the SARS-CoV-2-targeted, protease-inhibitor-focused and protein–protein-interactioninhibitor-focused libraries to gain a better understanding of how these libraries were designed. The
most common were ligand- and structure-based approaches, along with various filtering steps, using
molecular descriptors. Often, these methods were combined to obtain the final library. We recognized
the abundance of targeted libraries offered and complimented by the inclusion of analytical data;
however, serious concerns had to be raised. Namely, vendors lack the information on the library
design and the references to the primary literature. Few references to active compounds were also
provided when using the ligand-based design and usually only protein classes or a general panel
of targets were listed, along with a general reference to the methods, such as molecular docking for
the structure-based design. No receptor data, docking protocols or even references to the applied
molecular docking software (or other HTVS software), and no pharmacophore or filter design
details were given. No detailed functional group or chemical space analyses were reported, and no
specific orientation of the libraries toward the design of covalent or noncovalent inhibitors could
be observed. All libraries contained pan-assay interference compounds (PAINS), rapid elimination
of swill compounds (REOS) and aggregators, as well as focused on the drug-like model, with the
majority of compounds possessing their molecular mass around 500 g/mol. These facts do not bode
well for the use of the reviewed libraries in drug design and lend themselves to commercial drug
companies to focus on and improve. |
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| Keywords: | targeted libraries, focused libraries, computer-aided drug design, virtual screening, in silico drug design, high-throughput virtual screening |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 07.12.2021 |
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| Article acceptance date: | 28.12.2021 |
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| Publication date: | 30.12.2021 |
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| Publisher: | MDPI |
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| Year of publishing: | 2022 |
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| Number of pages: | 22 str. |
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| Numbering: | Vol. 23, no. 1 |
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| PID: | 20.500.12556/DKUM-92444  |
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| UDC: | 577 |
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| ISSN on article: | 1422-0067 |
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| COBISS.SI-ID: | 92031235 |
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| DOI: | 10.3390/ijms23010393 |
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| Copyright: | © 2021 by the authors |
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| Publication date in DKUM: | 09.04.2025 |
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| Views: | 180 |
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| Downloads: | 11 |
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| Metadata: |    |
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| Categories: | Misc.
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