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

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dc.contributor.authorTolksdorf, Beatrice
dc.contributor.authorNie, Chuanxiong
dc.contributor.authorNiemeyer, Daniela
dc.contributor.authorRöhrs, Viola
dc.contributor.authorBerg, Johanna
dc.contributor.authorLauster, Daniel
dc.contributor.authorAdler, Julia M.
dc.contributor.authorHaag, Rainer
dc.contributor.authorTrimpert, Jakob
dc.contributor.authorKaufer, Benedikt
dc.contributor.authorDrosten, Christian
dc.contributor.authorKurreck, Jens
dc.date.accessioned2021-11-05T10:35:53Z
dc.date.available2021-11-05T10:35:53Z
dc.date.issued2021-10-08
dc.date.updated2021-11-04T21:21:53Z
dc.description.abstractSevere 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.en
dc.description.sponsorshipDFG, 414044773, Open Access Publizieren 2021 - 2022 / Technische Universität Berlinde
dc.identifier.eissn1999-4915
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/13816
dc.identifier.urihttp://dx.doi.org/10.14279/depositonce-12592
dc.language.isoenen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subject.ddc540 Chemie und zugeordnete Wissenschaftende
dc.subject.otherSARS-CoV-2en
dc.subject.otherCOVID-19en
dc.subject.otherRNAi therapyen
dc.subject.othersiRNAen
dc.subject.other5′-UTRen
dc.subject.otherleader sequenceen
dc.titleInhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequenceen
dc.typeArticleen
dc.type.versionpublishedVersionen
dcterms.bibliographicCitation.articlenumber2030en
dcterms.bibliographicCitation.doi10.3390/v13102030en
dcterms.bibliographicCitation.issue10en
dcterms.bibliographicCitation.journaltitleVirusesen
dcterms.bibliographicCitation.originalpublishernameMDPIen
dcterms.bibliographicCitation.originalpublisherplaceBaselen
dcterms.bibliographicCitation.volume13en
tub.accessrights.dnbfreeen
tub.affiliationFak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Angewandte Biochemiede
tub.affiliation.facultyFak. 3 Prozesswissenschaftende
tub.affiliation.groupFG Angewandte Biochemiede
tub.affiliation.instituteInst. Biotechnologiede
tub.publisher.universityorinstitutionTechnische Universität Berlinen

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