Suppression of SARS-CoV-2 Replication with Stabilized and Click- Chemistry Modified siRNAs
2022-07-08
Franziska R. Traube, Marcel Stern, Annika J. Tölke, Martina Rudelius, Ernesto Mejías-Pérez, Nada Raddaoui, Beate M. Kümmerer, Céline Douat, Filipp Streshnev, Manuel Albanese, Paul R. Wratil, Yasmin V. Gärtner, Milda Nainytė, Grazia Giorgio, Stylianos Michalakis, Sabine Schneider, Hendrik Streeck, Markus Müller, Oliver T. Keppler, and Thomas Carell
Angew. Chem. Int. Ed., 61, e202204556, 2022
The emergence of more transmissible or aggressive variants of SARS-CoV-2 requires the development of antiviral medication that is quickly adjustable to evolving viral escape mutations. Here we report the synthesis of chemically stabilized small interfering RNA (siRNA) against SARS-CoV-2. The siRNA can be further modified with receptor ligands such as peptides using CuI-catalysed click-chemistry. We demonstrate that optimized siRNAs can reduce viral loads and virus-induced cytotoxicity by up to five orders of magnitude in cell lines challenged with SARS-CoV-2. Furthermore, we show that an ACE2-binding peptide-conjugated siRNA is able to reduce virus replication and virus-induced apoptosis in 3D mucociliary lung microtissues. The adjustment of the siRNA sequence allows a rapid adaptation of their antiviral activity against different variants of concern. The ability to conjugate the siRNA via click-chemistry to receptor ligands facilitates the construction of targeted siRNAs for a flexible antiviral defence strategy.
Speaker: Prof. Dr. Thomas Carell
Ludwig-Maximilians-Universität München
Institut für Chemische Epigenetik (ICEM)
Department of Chemistry
Office:
Würmtalstrasse 201
81377 Munich
Germany
Mailing address:
Butenandtstr. 5 - 13
81377 Munich
Germany
Phone: +49 (0)89 2180-77750
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Management: Dr. Nada Raddaoui
Institute for Chemical Epigenetics Munich (ICEM)
Office:
Würmtalstrasse 201, Building L, Room 03.004
81377 Munich
Germany
Mailing address:
Butenandtstr. 5 - 13
81377 Munich
Germany
Phone: +49 (0)89 2180-77755
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Secretary: Birgit Carell
Institute for Chemical Epigenetics Munich (ICEM)
Office:
Würmtalstrasse 201, Building L, Room 00.007
81377 Munich
Germany
Mailing address:
Butenandtstr. 5 - 13
81377 Munich
Germany
Phone: +49 (0)89 2180-77751
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website support: Martina Schuster
Prof. Dr. Lena Daumann
LMU Munich
Department of Chemistry
Butenandtstr. 5 - 13
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81377 Munich, Germany
Phone: +49 89 2180 77486
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Dr. Sabine Schneider
LMU Munich
Institute for Chemical Epigenetics
Butenandtstr. 5 - 13
House L
81377 Munich, Germany
Phone: +49 89 2180 77716
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Dr. Martin Sumser (Coordinator)
LMU Munich
Institute for Chemical Epigenetics
Butenandtstr. 5 - 13
House L
81377 Munich, Germany
Phone: +49 89 2180 77765
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