Novel Inhalable COVID-19 Therapeutic Targeting Viral Replication

Scientists from the University of California, Berkeley have announced the invention of new COVID-19 therapeutics as easy as a nasal spray. The novel therapeutic strategy targeting the SARS-CoV-2 RNA using locked nucleic acid antisense oligonucleotides (LNA ASOs) was published in the journal Nature Communication on 3 Aug. 

Although various vaccines are available in the market, it was not so reachable globally due to the needs of cold chain transportation and health care professionals. Hence, the team intended to create an alternative that is cheaply available everywhere with the ability to reduce infection risk or prevent critical conditions.

Related article: Inhaling Immunity: UNC Research on Inhalable COVID Vaccines

How Does ASO Work?

Like DNA, RNA carries genetic information coded in a sequence of bases—but unlike DNA, RNA usually comes in a single strand, without a complementary strand to form a double helix. However, RNA still readily binds to complementary base pair sequences. ASOs are short strands of lab-made base pair sequences that are designed to stick to specific parts of RNA in viruses and cells.

The LNA ASO identified could bind to the 5′ leader sequence of SARS-CoV-2 thus effectively preventing viral replication in human cells. It is believed to be efficacious in countering all SARS-CoV-2 “variants of concern” as it targets the highly preserved stem-loop structure of the virus, which makes it stand out from other nasal prophylactics aiming at spike protein which easily mutated. As expected, daily intranasal administration of this LNA ASO in the COVID-19 mouse model suppresses viral replication (>80-fold) in the lungs of infected mice.

Its chemical stability, and relatively low large-scale production cost, make it ideal for treating COVID-19 infections in areas of the world lacking electricity or refrigeration. Moreover, its production is rather simplified if compared to siRNA-based SARS-CoV-2 therapy which would prevent the risk of off-target inflammatory responses. The non-invasive nature represents a promising user-friendly therapeutic strategy for virus-induced respiratory diseases such as COVID-19. 

New Antiviral Therapy for RNA Viruses

The team has additional experiments to conduct before the clinical trials start. If the treatment proves to be safe and effective in humans, the ASO technology could be readily modified to target other RNA viruses, such as influenza viruses, which also have pandemic potential. The design flexibility to specifically target highly conserved and critical regulatory regions of the viral genome would definitely push antiviral therapy to the next level.

Author

Nai Ye Yeat