Targeting the Conserved Stem Loop 2 Motif in the SARS-CoV-2 Genome
| Autor: | Rachel Ulferts, William G. Scott, Yiliang Ding, Mary Wu, Nicole Doyle, Helena J. Maier, Felix Randow, Michal P. Wandel, Xiaofei Yang, Ben F. Luisi, Stephanie Oerum, Sara M. O'Rourke, Rupert Beale, Kotryna Bloznelyte, Valeria Lulla, Tom Dendooven, Katarzyna J Bandyra, Andrew E. Firth |
|---|---|
| Přispěvatelé: | Lulla, Valeria [0000-0002-6605-0727], Bandyra, Katarzyna [0000-0003-2607-6700], Firth, Andrew [0000-0002-7986-9520], Luisi, Ben [0000-0003-1144-9877], Apollo - University of Cambridge Repository, Pfeiffer, Julie K |
| Rok vydání: | 2021 |
| Předmět: |
Untranslated region
RNA Folding viruses coronavirus medicine.disease_cause Virus Replication Medical and Health Sciences Conserved sequence astrovirus 0302 clinical medicine Chlorocebus aethiops Viral Replicon Lung Coronavirus Subgenomic mRNA Genetics s2m 0303 health sciences Genome virus diseases gapmer Biological Sciences Stem-loop Infectious Diseases 030220 oncology & carcinogenesis RNA Viral Infection Biotechnology Immunology Genome Viral Biology Microbiology Vaccine Related 03 medical and health sciences Biodefense Virology Vaccines and Antiviral Agents medicine Animals Humans Nucleotide Motifs Vero Cells 030304 developmental biology therapeutic oligonucleotides Agricultural and Veterinary Sciences SARS-CoV-2 Prevention plus-strand RNA virus RNA COVID-19 Pneumonia Emerging Infectious Diseases LNA HEK293 Cells Viral replication Insect Science |
| Zdroj: | Journal of Virology J Virol Journal of virology, vol 95, iss 14 |
| ISSN: | 0022-538X |
| DOI: | 10.1128/jvi.00663-21 |
| Popis: | RNA structural elements occur in numerous single-stranded positive-sense RNA viruses. The stem-loop 2 motif (s2m) is one such element with an unusually high degree of sequence conservation, being found in the 3' untranslated region (UTR) in the genomes of many astroviruses, some picornaviruses and noroviruses, and a variety of coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. The evolutionary conservation and its occurrence in all viral subgenomic transcripts imply a key role for s2m in the viral infection cycle. Our findings indicate that the element, while stably folded, can nonetheless be invaded and remodeled spontaneously by antisense oligonucleotides (ASOs) that initiate pairing in exposed loops and trigger efficient sequence-specific RNA cleavage in reporter assays. ASOs also act to inhibit replication in an astrovirus replicon model system in a sequence-specific, dose-dependent manner and inhibit SARS-CoV-2 replication in cell culture. Our results thus permit us to suggest that the s2m element is readily targeted by ASOs, which show promise as antiviral agents. IMPORTANCE The highly conserved stem-loop 2 motif (s2m) is found in the genomes of many RNA viruses, including SARS-CoV-2. Our findings indicate that the s2m element can be targeted by antisense oligonucleotides. The antiviral potential of this element represents a promising start for further research into targeting conserved elements in RNA viruses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|