Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development
(2022) In Angewandte Chemie - International Edition 61(46).- Abstract
- SARS-CoV-2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti-virals. Within the international Covid19-NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these... (More)
- SARS-CoV-2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti-virals. Within the international Covid19-NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR-detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure-based drug design against the SCoV2 proteome. © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4237954a-2ea6-4017-a78f-d98a5b168628
- author
- Berg, Hannes ; Schwalbe, Harald and Robertson, Angus LU
- author collaboration
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- keywords
- COVID19-NMR, Drug Discovery, Fragment Screening, NMR Spectroscopy, Protein, SARS-CoV-2
- in
- Angewandte Chemie - International Edition
- volume
- 61
- issue
- 46
- article number
- e202205858
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85139756352
- ISSN
- 1521-3773
- DOI
- 10.1002/anie.202205858
- language
- English
- LU publication?
- no
- id
- 4237954a-2ea6-4017-a78f-d98a5b168628
- date added to LUP
- 2024-01-30 09:13:21
- date last changed
- 2024-01-30 09:15:22
@article{4237954a-2ea6-4017-a78f-d98a5b168628, abstract = {{SARS-CoV-2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti-virals. Within the international Covid19-NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR-detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure-based drug design against the SCoV2 proteome. © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.}}, author = {{Berg, Hannes and Schwalbe, Harald and Robertson, Angus}}, issn = {{1521-3773}}, keywords = {{COVID19-NMR; Drug Discovery; Fragment Screening; NMR Spectroscopy; Protein; SARS-CoV-2}}, language = {{eng}}, number = {{46}}, publisher = {{John Wiley & Sons Inc.}}, series = {{Angewandte Chemie - International Edition}}, title = {{Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development}}, url = {{http://dx.doi.org/10.1002/anie.202205858}}, doi = {{10.1002/anie.202205858}}, volume = {{61}}, year = {{2022}}, }