Bojkova, Denisa, Steinhorst, Katja, Bechtel, Marco, Zoeller, Nadja, Doll, Monika, Ott, Melanie, Rothweiler, Florian, Rothenburger, Tamara, Riecken, Kristoffer, Fehse, Boris, and others. (2026) Discovery of synthetic G-quadruplex DNA as SARS-CoV-2 helicase inhibitor with antiviral, anti-inflammatory and antioxidative properties. Cell Death Discovery, 12 . Article Number 159. ISSN 2058-7716. (doi:10.1038/s41420-026-03006-0) (KAR id:113650)
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| Official URL: https://doi.org/10.1038/s41420-026-03006-0 |
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Abstract
SARS-CoV-2 RNA contains guanine-rich sequences that form secondary structures known as G quadruplexes (G4s). The SARS-CoV-2 nonstructural protein (NSP13) resolves G4s due to its helicase and ATPase activity, a process essential for viral replication. Here, we tested the effects of synthetic G4s on SARS-CoV-2 replication. In agreement, a synthetic G4 DNA 20 mer, consisting exclusively of guanines linked by a phosphorothioate backbone (designated GQ20-PTO), inhibited the replication of various SARS-CoV-2 variants in human lung cell cultures. Mechanistically, GQ20-PTO bound to NSP13 and inhibited its helicase and ATPase activity. Independent of its antiviral effects, GQ20-PTO additionally suppressed IFNβ and IL-6 (but not TNFα) signaling and the formation of reactive oxygen species, processes known to contribute to hyperinflammation in severe COVID-19. Hence, G4 quadruplexes like GQ20-PTO represent a novel class of DNA-based compounds for COVID-19 treatment with the potential to interfere with both SARS-CoV-2 replication and the uncontrolled inflammation associated with life-threatening COVID-19.
| Item Type: | Article |
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| DOI/Identification number: | 10.1038/s41420-026-03006-0 |
| Subjects: | Q Science |
| Institutional Unit: | Schools > School of Natural Sciences > Biosciences |
| Former Institutional Unit: |
There are no former institutional units.
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| Funders: | Deutsche Forschungsgemeinschaft (https://ror.org/018mejw64) |
| SWORD Depositor: | JISC Publications Router |
| Depositing User: | JISC Publications Router |
| Date Deposited: | 01 Apr 2026 15:17 UTC |
| Last Modified: | 02 Apr 2026 15:17 UTC |
| Resource URI: | https://kar.kent.ac.uk/id/eprint/113650 (The current URI for this page, for reference purposes) |
University of Kent Author Information
Michaelis, Martin.
| Creator's ORCID: |
 https://orcid.org/0000-0002-5710-5888
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