Coronavirus Inhibitors Targeting nsp16
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Ejlal A Omer
- Sara Abdelfatah
- Max Riedl
- Christian Meesters
- Andreas Hildebrandt
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000930344800001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3390/molecules28030988
- eISSN
- 1420-3049
- Externe Identifier
- Clarivate Analytics Document Solution ID: 8V0QH
- PubMed Identifier: 36770656
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- MOLECULES
- Schlüsselwörter
- SARS-CoV-2
- SARS-CoV-1
- MERS-CoV
- nsp16
- natural products
- pan-inhibitor
- virtual drug screening
- Artikelnummer
- ARTN 988
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Titel
- Coronavirus Inhibitors Targeting nsp16
- Sub types
- Article
- Ausgabe der Zeitschrift
- 28
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:p>During the past three decades, humans have been confronted with different new coronavirus outbreaks. Since the end of the year 2019, COVID-19 threatens the world as a rapidly spreading infectious disease. For this work, we targeted the non-structural protein 16 (nsp16) as a key protein of SARS-CoV-2, SARS-CoV-1 and MERS-CoV to develop broad-spectrum inhibitors of nsp16. Computational methods were used to filter candidates from a natural product-based library of 224,205 compounds obtained from the ZINC database. The binding of the candidates to nsp16 was assessed using virtual screening with VINA LC, and molecular docking with AutoDock 4.2.6. The top 9 compounds were bound to the nsp16 protein of SARS-CoV-2, SARS-CoV-1, and MERS-CoV with the lowest binding energies (LBEs) in the range of −9.0 to −13.0 kcal with VINA LC. The AutoDock-based LBEs for nsp16 of SARS-CoV-2 ranged from −11.42 to −16.11 kcal/mol with predicted inhibition constants (pKi) from 0.002 to 4.51 nM, the natural substrate S-adenosyl methionine (SAM) was used as control. In silico results were verified by microscale thermophoresis as in vitro assay. The candidates were investigated further for their cytotoxicity in normal MRC-5 lung fibroblasts to determine their therapeutic indices. Here, the IC50 values of all three compounds were >10 µM. In summary, we identified three novel SARS-CoV-2 inhibitors, two of which showed broad-spectrum activity to nsp16 in SARS-CoV-2, SARS-CoV-1, and MERS-CoV. All three compounds are coumarin derivatives that contain chromen-2-one in their scaffolds.</jats:p>
- Autoren
- Ejlal A Omer
- Sara Abdelfatah
- Max Riedl
- Christian Meesters
- Andreas Hildebrandt
- Thomas Efferth
- DOI
- 10.3390/molecules28030988
- eISSN
- 1420-3049
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Molecules
- Sprache
- en
- Online publication date
- 2023
- Paginierung
- 988 - 988
- Status
- Published online
- Herausgeber
- MDPI AG
- Herausgeber URL
- http://dx.doi.org/10.3390/molecules28030988
- Datum der Datenerfassung
- 2023
- Titel
- Coronavirus Inhibitors Targeting nsp16
- Ausgabe der Zeitschrift
- 28
Data source: Crossref
- Abstract
- During the past three decades, humans have been confronted with different new coronavirus outbreaks. Since the end of the year 2019, COVID-19 threatens the world as a rapidly spreading infectious disease. For this work, we targeted the non-structural protein 16 (nsp16) as a key protein of SARS-CoV-2, SARS-CoV-1 and MERS-CoV to develop broad-spectrum inhibitors of nsp16. Computational methods were used to filter candidates from a natural product-based library of 224,205 compounds obtained from the ZINC database. The binding of the candidates to nsp16 was assessed using virtual screening with VINA LC, and molecular docking with AutoDock 4.2.6. The top 9 compounds were bound to the nsp16 protein of SARS-CoV-2, SARS-CoV-1, and MERS-CoV with the lowest binding energies (LBEs) in the range of -9.0 to -13.0 kcal with VINA LC. The AutoDock-based LBEs for nsp16 of SARS-CoV-2 ranged from -11.42 to -16.11 kcal/mol with predicted inhibition constants (pKi) from 0.002 to 4.51 nM, the natural substrate S-adenosyl methionine (SAM) was used as control. In silico results were verified by microscale thermophoresis as in vitro assay. The candidates were investigated further for their cytotoxicity in normal MRC-5 lung fibroblasts to determine their therapeutic indices. Here, the IC<sub>50</sub> values of all three compounds were >10 µM. In summary, we identified three novel SARS-CoV-2 inhibitors, two of which showed broad-spectrum activity to nsp16 in SARS-CoV-2, SARS-CoV-1, and MERS-CoV. All three compounds are coumarin derivatives that contain chromen-2-one in their scaffolds.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
- Autoren
- Ejlal A Omer
- Sara Abdelfatah
- Max Riedl
- Christian Meesters
- Andreas Hildebrandt
- Thomas Efferth
- DOI
- 10.3390/molecules28030988
- eISSN
- 1420-3049
- Externe Identifier
- PubMed Identifier: 36770656
- PubMed Central ID: PMC9920298
- Funding acknowledgements
- Frankfurt a. M.:
- Marc Strobel:
- CVC Capital Partners:
- Open access
- true
- ISSN
- 1420-3049
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Molecules (Basel, Switzerland)
- Schlüsselwörter
- Humans
- S-Adenosylmethionine
- Molecular Docking Simulation
- Middle East Respiratory Syndrome Coronavirus
- COVID-19
- SARS-CoV-2
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2023
- Open access status
- Open Access
- Paginierung
- 988
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2023
- Titel
- Coronavirus Inhibitors Targeting nsp16.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 28
Files
https://www.mdpi.com/1420-3049/28/3/988/pdf?version=1675222239 https://europepmc.org/articles/PMC9920298?pdf=render
Data source: Europe PubMed Central
- Abstract
- During the past three decades, humans have been confronted with different new coronavirus outbreaks. Since the end of the year 2019, COVID-19 threatens the world as a rapidly spreading infectious disease. For this work, we targeted the non-structural protein 16 (nsp16) as a key protein of SARS-CoV-2, SARS-CoV-1 and MERS-CoV to develop broad-spectrum inhibitors of nsp16. Computational methods were used to filter candidates from a natural product-based library of 224,205 compounds obtained from the ZINC database. The binding of the candidates to nsp16 was assessed using virtual screening with VINA LC, and molecular docking with AutoDock 4.2.6. The top 9 compounds were bound to the nsp16 protein of SARS-CoV-2, SARS-CoV-1, and MERS-CoV with the lowest binding energies (LBEs) in the range of -9.0 to -13.0 kcal with VINA LC. The AutoDock-based LBEs for nsp16 of SARS-CoV-2 ranged from -11.42 to -16.11 kcal/mol with predicted inhibition constants (pKi) from 0.002 to 4.51 nM, the natural substrate S-adenosyl methionine (SAM) was used as control. In silico results were verified by microscale thermophoresis as in vitro assay. The candidates were investigated further for their cytotoxicity in normal MRC-5 lung fibroblasts to determine their therapeutic indices. Here, the IC50 values of all three compounds were >10 µM. In summary, we identified three novel SARS-CoV-2 inhibitors, two of which showed broad-spectrum activity to nsp16 in SARS-CoV-2, SARS-CoV-1, and MERS-CoV. All three compounds are coumarin derivatives that contain chromen-2-one in their scaffolds.
- Date of acceptance
- 2023
- Autoren
- Ejlal A Omer
- Sara Abdelfatah
- Max Riedl
- Christian Meesters
- Andreas Hildebrandt
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/36770656
- DOI
- 10.3390/molecules28030988
- eISSN
- 1420-3049
- Externe Identifier
- PubMed Central ID: PMC9920298
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Molecules
- Schlüsselwörter
- MERS-CoV
- SARS-CoV-1
- SARS-CoV-2
- natural products
- nsp16
- pan-inhibitor
- virtual drug screening
- Humans
- COVID-19
- SARS-CoV-2
- Molecular Docking Simulation
- Middle East Respiratory Syndrome Coronavirus
- S-Adenosylmethionine
- Sprache
- eng
- Country
- Switzerland
- PII
- molecules28030988
- Datum der Veröffentlichung
- 2023
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2023
- Titel
- Coronavirus Inhibitors Targeting nsp16.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 28
Data source: PubMed
- Beziehungen:
- Property of