Publication Database

Inhibition of SARS-CoV-2 replication by a small interfering RNA targeting the leader sequence (2021)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Tolksdorf, Beatrice

Nie, Chuanxiong

Niemeyer, Daniela

Röhrs, Viola

Berg, Johanna

Lauster, Daniel

Adler, Julia M. (WE 5)

Haag, Rainer

Trimpert, Jakob (WE 5)

Kaufer, Benedikt (WE 5)

Drosten, Christian

Kurreck, Jens

Quelle

Viruses

Bandzählung: 13

Heftzählung: 10

Seiten: Artikel 2030

ISSN: 1999-4915

Sprache

Englisch

Verweise

URL (Volltext): https://www.mdpi.com/1999-4915/13/10/2030

DOI: 10.3390/v13102030

Pubmed: 34696460

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.