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10.1002/anie.202204556

http://scihub22266oqcxt.onion/10.1002/anie.202204556
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35802496!9350007!35802496
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suck abstract from ncbi


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pmid35802496      Angew+Chem+Int+Ed+Engl 2022 ; 61 (38): e202204556
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  • Suppression of SARS-CoV-2 Replication with Stabilized and Click-Chemistry Modified siRNAs #MMPMID35802496
  • Traube FR; Stern M; Tolke AJ; Rudelius M; Mejias-Perez E; Raddaoui N; Kummerer BM; Douat C; Streshnev F; Albanese M; Wratil PR; Gartner YV; Nainyte M; Giorgio G; Michalakis S; Schneider S; Streeck H; Muller M; Keppler OT; Carell T
  • Angew Chem Int Ed Engl 2022[Sep]; 61 (38): e202204556 PMID35802496show ga
  • 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 Cu(I) -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.
  • |*COVID-19[MESH]
  • |*SARS-CoV-2/genetics[MESH]
  • |Antiviral Agents/pharmacology[MESH]
  • |Humans[MESH]
  • |Ligands[MESH]
  • |RNA, Small Interfering/pharmacology[MESH]


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