Inhibition of SARS-CoV-2 coronavirus proliferation by designer antisense-circRNAs.
Nucleic Acids Res
; 49(21): 12502-12516, 2021 12 02.
Article
in English
| MEDLINE | ID: covidwho-1546005
ABSTRACT
Circular RNAs (circRNAs) are noncoding RNAs that exist in all eukaryotes investigated and are derived from back-splicing of certain pre-mRNA exons. Here, we report the application of artificial circRNAs designed to act as antisense-RNAs. We systematically tested a series of antisense-circRNAs targeted to the SARS-CoV-2 genome RNA, in particular its structurally conserved 5'-untranslated region. Functional assays with both reporter transfections as well as with SARS-CoV-2 infections revealed that specific segments of the SARS-CoV-2 5'-untranslated region can be efficiently accessed by specific antisense-circRNAs, resulting in up to 90% reduction of virus proliferation in cell culture, and with a durability of at least 48 h. Presenting the antisense sequence within a circRNA clearly proved more efficient than in the corresponding linear configuration and is superior to modified antisense oligonucleotides. The activity of the antisense-circRNA is surprisingly robust towards point mutations in the target sequence. This strategy opens up novel applications for designer circRNAs and promising therapeutic strategies in molecular medicine.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Replication
/
RNA, Viral
/
RNA, Antisense
/
Genome, Viral
/
RNA, Circular
/
SARS-CoV-2
Limits:
Animals
/
Humans
Language:
English
Journal:
Nucleic Acids Res
Year:
2021
Document Type:
Article
Affiliation country:
Nar
Similar
MEDLINE
...
LILACS
LIS