Publication Details |
| Category | Text Publication |
| Reference Category | Journals |
| DOI | 10.1002/cmdc.202100732 |
Licence  |
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| Title (Primary) | Andrographolide derivatives target the KEAP1/NRF2 axis and possess potent anti-SARS-CoV-2 activity |
| Author | Schulte, B.; König, M.; Escher, B.I.
; Wittenburg, S.; Proj, M.; Wolf, V.; Lemke, C.; Schnakenburg, G.; Sosič, I.; Streeck, H.; Müller, C.E.; Gütschow, M.; Steinebach, C. |
| Source Titel | ChemMedChem |
| Year | 2022 |
| Department | ZELLTOX |
| Volume | 17 |
| Issue | 5 |
| Page From | e202100732 |
| Language | englisch |
| Topic | T9 Healthy Planet |
| Supplements | https://chemistry-europe.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fcmdc.202100732&file=cmdc202100732-sup-0001-misc_information.pdf |
| Keywords | SARS-CoV-2; andrographolide; KEAP1/NRF2; natural products; medicinal chemistry |
| Abstract | Naturally occurring compounds represent a vast pool of pharmacologically active entities. One of such compounds is andrographolide, which is endowed with many beneficial properties, including the activity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). To initiate a drug repurposing or hit optimization campaign, it is imperative to unravel the primary mechanism(s) of the antiviral action of andrographolide. Here, we showed by means of a reporter gene assay that andrographolide exerts its anti-SARS-CoV-2 effects by inhibiting the interaction between Kelch-like ECH-associated protein 1 (KEAP1) and nuclear factor erythroid 2-related factor 2 (NRF2) causing NRF2 upregulation. Moreover, we demonstrated that subtle structural modifications of andrographolide could lead to derivatives with stronger on-target activities and improved physicochemical properties. Our results indicate that further optimization of this structural class is warranted to develop novel COVID-19 therapies. |
| Persistent UFZ Identifier | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=25731 |
| Schulte, B., König, M., Escher, B.I., Wittenburg, S., Proj, M., Wolf, V., Lemke, C., Schnakenburg, G., Sosič, I., Streeck, H., Müller, C.E., Gütschow, M., Steinebach, C. (2022): Andrographolide derivatives target the KEAP1/NRF2 axis and possess potent anti-SARS-CoV-2 activity ChemMedChem 17 (5), e202100732 10.1002/cmdc.202100732 |
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