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Article

Inhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequence

1
Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, 10623 Berlin, Germany
2
Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
3
German Centre for Infection Research (DZIF), Charitéplatz 1, 10117 Berlin, Germany
4
Institute of Virology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
5
Department of Veterinary Medicine, Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany
6
Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Bruno Coutard and Franck Touret
Viruses 2021, 13(10), 2030; https://doi.org/10.3390/v13102030
Received: 20 September 2021 / Revised: 4 October 2021 / Accepted: 6 October 2021 / Published: 8 October 2021
(This article belongs to the Special Issue Antiviral Therapeutics for Emerging Viruses)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide and led to approximately 4 million deaths as of August 2021. Despite successful vaccine development, treatment options are limited. A promising strategy to specifically target viral infections is to suppress viral replication through RNA interference (RNAi). Hence, we designed eight small interfering RNAs (siRNAs) targeting the highly conserved 5′-untranslated region (5′-UTR) of SARS-CoV-2. The most promising candidate identified in initial reporter assays, termed siCoV6, targets the leader sequence of the virus, which is present in the genomic as well as in all subgenomic RNAs. In assays with infectious SARS-CoV-2, it reduced replication by two orders of magnitude and prevented the development of a cytopathic effect. Moreover, it retained its activity against the SARS-CoV-2 alpha variant and has perfect homology against all sequences of the delta variant that were analyzed by bioinformatic means. Interestingly, the siRNA was even highly active in virus replication assays with the SARS-CoV-1 family member. This work thus identified a very potent siRNA with a broad activity against various SARS-CoV viruses that represents a promising candidate for the development of new treatment options. View Full-Text
Keywords: SARS-CoV-2; COVID-19; RNAi therapy; siRNA; 5′-UTR; leader sequence SARS-CoV-2; COVID-19; RNAi therapy; siRNA; 5′-UTR; leader sequence
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MDPI and ACS Style

Tolksdorf, B.; Nie, C.; Niemeyer, D.; Röhrs, V.; Berg, J.; Lauster, D.; Adler, J.M.; Haag, R.; Trimpert, J.; Kaufer, B.; Drosten, C.; Kurreck, J. Inhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequence. Viruses 2021, 13, 2030. https://doi.org/10.3390/v13102030

AMA Style

Tolksdorf B, Nie C, Niemeyer D, Röhrs V, Berg J, Lauster D, Adler JM, Haag R, Trimpert J, Kaufer B, Drosten C, Kurreck J. Inhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequence. Viruses. 2021; 13(10):2030. https://doi.org/10.3390/v13102030

Chicago/Turabian Style

Tolksdorf, Beatrice, Chuanxiong Nie, Daniela Niemeyer, Viola Röhrs, Johanna Berg, Daniel Lauster, Julia M. Adler, Rainer Haag, Jakob Trimpert, Benedikt Kaufer, Christian Drosten, and Jens Kurreck. 2021. "Inhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequence" Viruses 13, no. 10: 2030. https://doi.org/10.3390/v13102030

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