Researchers from the USA and Denmark have described a new therapeutic option that targets the SARS-CoV-2 ribonucleic acid (RNA) using locked nucleic acid antisense oligonucleotides (LNA ASOs). They identified an LNA ASO that binds to the 5’ leader sequence of SARS-CoV-2 ORF1a/b. This disrupts a highly conserved stem-loop structure with nanomolar efficacy and inhibits viral replication in host cells. The results of the study are currently published on a pre-print server. The LNA ASO, when administered intranasally every day in the K18-hACE2 humanized COVID-19 mouse model, strongly (98-99%) suppressed viral replication in the lungs of the SARS-CoV-2-infected mice.
This reveals potent prophylactic as well as treatment effects of LNA ASOs. The researchers found that the LNA ASO also inhibits viral infection in golden Syrian hamsters and is effective against all SARS-CoV-2 variants of concern. LNA ASOs can override the challenge of viral mutations thanks to their ability to design sequences that are specifically targeted to highly conserved and key regulatory regions of the viral genome. In addition, LNA ASO cocktails that target multiple critical regions of the viral genome may further improve the efficacy of LNA ASOs as therapeutic candidates to overcome viral mutations. Given the relatively small size of RNA viral genomes and the ability to rapidly sequence any genome using next-generation sequencing techniques, anti-viral LNA ASOs can be designed and screened in a fast and efficient manner that allows rapid response to all kinds of health crises.
LNA ASOs are chemically stable compounds and can be modified to target various viral RNA sequences. They can be more impactful in remote areas where vaccine distribution is challenging, and they could also be stockpiled for use during other pandemics caused by coronaviruses that may threaten humanity in the future.
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