The rapid development of vaccines and treatments for COVID-19 has been one of the most significant scientific achievements in recent history. However, current treatments are not effective for all patients and COVID-19 still has a sizable mortality rate worldwide.
A recent study published in Antiviral Research describes a new treatment using short interfering RNA (siRNA) to effectively target human and animal SARS-CoV-1/2 genomes, creating a broad spectrum antiviral effect. This therapy needs no involvement from the immune system, meaning this could be of particular benefit to immunocompromised patients.
Learning to live with it
Current global COVID-19 management strategies heavily rely on regular vaccinations and post-infection immunity. However, over time, healthcare directives have generally changed from aiming to eliminate the virus, to finding a way to live with it.
Although most can accept that the risk of COVID-19 is not going away anytime soon, the regular emergence of new and more aggressive variants poses an issue around the current lack of broad-spectrum, direct action antiviral therapies that are efficient against the full range of variants. This is of most concern for immunocompromised and immunosuppressed individuals who do not generate robust immune responses following vaccination and are therefore at greater risk of a severe and life-threatening COVID-19 infection.
A universal treatment
RNA interference (RNAi) therapeutics induced by short interfering RNAs (siRNAs) offer a promising antiviral treatment option, with broad-spectrum antiviral capabilities unparalleled by current antiviral therapeutics. Researchers at the University of New South Wales in Sydney, Australia, have used novel siRNAs targeting highly conserved regions of the SARS-CoV-1 and 2 genomes to protect against virus-mediated cell death in cell line experiments. These siRNAs induce transcriptional or post-transcriptional gene silencing using RNA interference (RNAi) to target both the immunogenic and non-immunogenic regions of the genome, inhibiting the virus’ ability to replicate.
This siRNA treatment was found to protect cells from eight common SARS-CoV-2 variants with over 97% cell survival, a figure significantly higher than the currently used antivirals sotrovimab and remdesivir. As the siRNA treatment directly targets the virus itself, no immune cell involvement is required, meaning a patient would not need a functioning immune system for the treatment to be effective. Therefore, this is an exciting prospect for protection of high risk, immunocompromised patients for whom vaccines and other treatments may not be effective.
One step ahead
This study demonstrates the potential of siRNA use as a highly effective and broad-spectrum antiviral against multiple SARS-CoV-2 variants, including those resistant to antivirals and vaccine-generated neutralizing antibodies.
This could signify a breakthrough in the future treatment of high risk COVID-19 patients, as this therapy is expected to be effective against all current and future variants. “A very exciting promise of siRNA is that it has the potential to be a treatment option available prior to the emergence of new variants, keeping us one step ahead of this ever-changing virus”, states Dr Chantelle Ahlenstiel, principal investigator of the group based at the Kirby Institute, UNSW.
The therapy is still in pre-clinical development, with the next step being to measure its success in mouse models. However, the group are optimistic about its performance and hope to see progression through clinical trials and subsequent clinical integration for COVID-19 treatment over the next few years.