| Title: | Novel small-molecule inhibitors of the SARS-CoV-2 spike protein binding to neuropilin 1 |
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| Authors: | ID Kolarič, Anja (Author)
ID Jukič, Marko (Author)
ID Bren, Urban (Author) |
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| Files: |  pharmaceuticals-15-00165-v2.pdf (6,27 MB)
MD5: B82CA77FA0906A8506807CA8247AE1BD
 https://www.mdpi.com/1424-8247/15/2/165
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| Language: | English |
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| Work type: | Article |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: | FKKT - Faculty of Chemistry and Chemical Engineering
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| Abstract: | Furin cleavage of the SARS-CoV-2 spike protein results in a polybasic terminal sequence
termed the C-end rule (CendR), which is responsible for the binding to neuropilin 1 (NRP1), enhancing
viral infectivity and entry into the cell. Here we report the identification of 20 small-molecule
inhibitors that emerged from a virtual screening of nearly 950,000 drug-like compounds that bind
with high probability to the CendR-binding pocket of NRP1. In a spike NRP1 binding assay, two of
these compounds displayed a stronger inhibition of spike protein binding to NRP1 than the known
NRP1 antagonist EG00229, for which the inhibition of the CendR peptide binding to NRP1 was
also experimentally confirmed. These compounds present a good starting point for the design of
small-molecule antagonists against the SARS-CoV-2 viral entry. |
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| Keywords: | neuropilin 1, SARS-CoV-2, COVID-19, spike binding inhibitors, virtual screening, small-molecule antagonists, molecular docking, in vitro binding assay |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 29.10.2021 |
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| Article acceptance date: | 26.01.2022 |
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| Publication date: | 28.01.2022 |
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| Publisher: | MDPI, Molecular Diversity Preservation International |
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| Year of publishing: | 2022 |
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| Number of pages: | 14 str. |
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| Numbering: | Vol. 15, no. 2 |
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| PID: | 20.500.12556/DKUM-92745  |
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| UDC: | 577 |
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| ISSN on article: | 1424-8247 |
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| COBISS.SI-ID: | 95574275 |
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| DOI: | 10.3390/ph15020165 |
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| Copyright: | © 2022 by the authors |
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| Publication date in DKUM: | 09.05.2025 |
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| Views: | 166 |
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| Downloads: | 16 |
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| Metadata: |    |
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| Categories: | Misc.
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