Potential COVID treatment reduces viral count in mice lungs by 99.9%

An antiviral therapy is offering fresh hope as a potential treatment for COVID-19.
 
The therapy uses gene silencing RNA technology called siRNA (small-interfering RNA) to attack the SARS-CoV-2 virus’ genome directly.
 
These RNA medicines are then inserted into lipid nanoparticles, which are injected into the bloodstream and target cells with SARS-CoV-2.
 
Once the medication binds to the genome of the coronavirus, it destroys the virus.


The next-generation antiviral approach uses gene-silencing RNA technology to attack the virus’ genome directly, which stops the virus from replicating. 

Professor Nigel McMillan, Program Director of Infectious Diseases and Immunology at the Menzies Health Institute and Griffith University, is part of an international team of scientists that helped develop this new therapy.
 
He told newsGP the treatment, which has so far only been tested in mice, is looking promising.
 
‘We’ve got very good, strong pre-clinical data to show this is quite effective and we don’t see any red flags, so our clear next step is to move into the clinical trial space and that’s what we’ll be doing,’ he said.
 
Professor McMillan says the nanoparticles that contain the siRNA targets cells affected by SARS-CoV-2, with around one third of the load going to the lungs.
 
‘And it goes into every lung cell,’ Professor McMillan said.
 
‘It’s basically designed to bind [to] the genome of the coronavirus and when it does that it causes it to be destroyed, essentially cut up, and the cellular processes then digest the rest of the genome.’
 
While the treatment destroys SARS-CoV-2, it does not affect normal cells.
 
‘In normal cells it doesn’t do anything because it can’t find that piece of genome [of COVID-19] because the virus isn’t there,’ he said.
 
‘It’s really precise; precision medicine. It’s harmless to normal cells.’
 
The therapy is also scalable and cost-effective, Professor McMillan says, as nanoparticles are stable at 4°C for 12 months and at room temperature for more than one month, meaning it can be used in low-resource settings to treat infected patients.
 
This new therapy has been tested in mice infected with SARS-CoV-2, comparing outcomes to control groups, and the research has been published in Molecular Therapy on 13 May.
 
Professor McMillan says the research found that the mice that received the gene silencing RNA treatment displayed a ‘very much improved’ survival rate than those that did not receive this treatment.
 
‘We can see that the amount of virus left in their lungs is reduced compared to untreated mice by, in this case 99.9%,’ he said.
 
‘We get a vast reduction in the virus counts in the lungs of the mice, and of course what happens is they don’t suffer from the pneumonia and the side effects you get when you have such a viral infection, and they survive.’
 
Professor McMillan is hopeful this will translate to similar results in humans.
 
He says the use of RNA medicine is proving effective in vaccines against COVID-19, such as those developed by Pfizer and Moderna, and that the gene silencing technology has been used in humans to treat amyloidosis.
 
‘So we know it can go into humans from that point of view,’ he said.
 
Thomas Preiss, a Professor of RNA Biology at the Department of Genome Sciences at the Australian National University, told newsGP this is a ‘really timely and smart’ application of RNA interference technology.
 
‘Although the world now has vaccines to immunise populations against COVID-19, there [is] still … an urgent need for live-saving therapy for patients with serious COVID-19 infection,’ he said.
 
Professor Preiss says this study illustrates the ‘rich potential’ of RNA technology and that it works with the premise that, as an RNA virus, SARS-CoV-2 should be ‘highly vulnerable’ to RNA interference.
 
Meanwhile, the use of lipid nanoparticles to deliver siRNA into the lungs is also ‘highly effective’, and consequently, he believes this therapy promises to be a ‘very effective treatment’ for patients at risk of severe lung complications from COVID-19. 


The Griffith University COVID-19 antiviral therapy research team (l-r) Professor Kevin Morris, Dr Adi Idris, Professor Nigel McMillan, Dr Arron Supramanin and Mr Yusif Idres. (Image: Griffith University)
 
While the therapy proved effective in mice, Professor McMillan says the next step is to move on to clinical trials in humans, which could begin this year should they receive funding.
 
He also does not anticipate any side effects or safety issues will be found in clinical trials.
 
‘We’ve certainly done a lot of testing in animals and we wouldn’t expect there to be anything more than perhaps a fever,’ he said.
 
‘But we will have to wait and see of course as to what happens.
 
‘We’re hopeful; there’s no particular reason this shouldn’t turn into a viable therapy.’
 
If the drug passes clinical trial testing, it is likely to be administered as an intravenous therapy; Professor McMillian believes it is superior to intranasal for respiratory viral infections as inflammation is less of an issue when injecting a drug directly into the bloodstream.
 
‘We would envisage daily treatment for three to four days might be the way,’ he said. ‘An infusion’s probably another way to do it.
 
‘We haven’t yet determined what works best and that’s what the trials will tell us.’
 
Professor McMillan also says the treatment would need to be given to patients early on in their illness, but that any trials could help determine ‘how late’ the drug could be delivered and still be effective.
 
‘I would envisage that, like all antivirals – so, if we think of drugs like Tamiflu, for example – the earlier you get it into someone, the better the outcome,’ he said.
 
Professor McMillan believes the use of this RNA medication against COVID-19 may be a game-changer for the pandemic, as current therapeutic avenues for COVID-19 are limited.
 
While dexamethasone ‘clearly works’ for the acute respiratory syndrome that can develop around day 10 of COVID-19, he says it is also a ‘sledgehammer’ approach in terms of suppressing the immune system, and allows the virus to replicate more.
 
Professor McMillan says the pre-clinical data on this therapy also shows it is ‘far superior’ to treatment of COVID-19 with remdesivir, which is desperately needed.
 
‘We have good vaccines now, and that problem’s pretty much solved, but we don’t have good antiviral treatment, and this is where the efforts are concentrated now,’ he said.
 
‘It’s really a problem that needs solving sooner rather than later, because the virus isn’t going away.’
 
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