While public health announcements focus on the Hands, Face, Space message and the worldwide vaccine roll out aims to curb new cases, we have neglected to keep up with research into new treatments for those who contract covid-19.
When covid-19 sent the world into lockdowns in March 2020, new research was everywhere. Studies looked at vitamin deficiency, plasma therapy, our immune response, and ventilation to name a few areas. One focal point, which had a lot of press early in the pandemic, was antiviral treatments, specifically those which could be repurposed. Every news agency was reporting on drugs like Dexamethasone and Remdesivir; a concoction of treatments the then US president, Donald Trump, was said to be taking to ward off COVID. What are antivirals and how can they help covid-19 sufferers?
Of the drugs which hit the headlines, Dexamethasone is a steroid (so we won’t be focusing on that in this article), but Remdesivir is an antiviral. Antivirals are simply drugs which target viral infections, either killing or preventing further growth of the virus in question. You may have previously heard of Tamiflu, the antiviral used against the flu virus, which was prescribed more widely during the swine flu outbreak in 2009. In this piece from the BBC, in 2014, they reported on the UK government stockpiling Tamiflu to prepare for a future pandemic… While antivirals do not cure viral infections, and are not given to those with mild infections, such drugs can help alleviate symptoms and aid a faster recovery for individuals who suffer with more severe symptoms. If effective, antivirals are used for covid-19 sufferers, potentially reducing the number of patients requiring ICU beds/ventilation and shortening the time it takes to recover, freeing hospital capacity. Remdesivir was first developed as an antiviral treatment for Ebola. It is chemically similar to the materials the virus needs to replicate, essentially confusing the virus and disrupting its ability to replicate. For use in covid-19 patients, trials using Remdesivir showed a reduction in the duration of symptoms from 15 to 11 days, but provided no evidence for saving lives. Researchers found it was most effective when given early on in the course of an infection, not necessarily helpful to those who need ICU. Drug design programmes can take up to 20 years to get a new drug to market, but by repurposing drugs which already have medical approval (such as Remdesivir), we can drastically reduce the time it takes to be used in the population; which can be lifesaving if the drug is highly effective.
So, why are there not more antivirals on offer other than Remdesivir? Viruses depend on our cells in order to replicate and therefore antivirals have a very difficult task: stop the virus without harming the bodies healthy cells. However, as scientists learn more about a virus’ life cycle, it becomes easier to specifically target the virus and avoid healthy cells. To replicate, a virus must attach to, and get inside a “host cell” (e.g. a healthy human cell). Here, the virus tricks the host cell into copying its viral genes and leads to creation of new virus cells which can then leave the original host cell to infect new cells. Antivirals often mimic host cells to interfere with a viral life cycle. Therefore, the earlier you take an antiviral drug, the better, as there is less virus to “mop up”. Viruses are difficult targets though. Unlike bacteria, which are independent living cells that provide lots of cellular pathways and unique features to target, viruses depend on our cells to act as hosts and provide proteins the virus needs for replication. Also, much like the problems arising with antibiotic resistance, viruses aren’t immune from developing antiviral resistance either.
One success story is that of antivirals used to treat HIV, of which there are 30 or more drugs to select from. So, although we do not currently have a vast selection to choose from, there is hope for antiviral drugs used against covid-19. Just this month, reports of clinical trials for new covid-19 antivirals are springing up across the corners of the internet. In February, scientists at the University of Nottingham published work on a broad spectrum (i.e. targets more than one type of virus) antiviral called thapsigargin. While still in the early stages of research, and with more testing required, thapsigargin was shown to be several hundred times more effective than current antiviral options for covid-19 and could be given in pill form (whereas, Remdesivir is injected). Then you have two pharma giants, Pfizer and Merck, both working on their own antiviral drugs. Whilst also helping individuals shortly after the appearance of symptoms, Pfizer’s antiviral also aims to be used for those experiencing long covid-19, preventing long-term shedding of the virus and therefore potential transmission to others. Merck however, have been working on molnupiravir, another broad spectrum antiviral and began discussion about this drug in January 2020 (find the full story HERE). Molnupiravir introduces errors into the covid-19’s RNA sequence which are then replicated until it no longer functions. However, as you do not know where the errors are being added, they could find their way into our systems and other drugs with the same main ingredient as molnupiravir have previously been abandoned due to concerns over birth defects.
One project I’ve been closely following is COVID Moonshot, a “crowdsourced initiative to accelerate the development of a COVID antiviral“, working without intellectual property constraints. Most amazingly though, they use cutting-edge machine learning tools and computational chemistry to aid drug design. (I hope to write a follow up article about their work soon…). Since their first roll outs began late in 2020, attention has been driven towards the covid-19 vaccines. However, many believe we need a multifaceted approach to alleviate the strain of the pandemic, and that means using antivirals. Whilst antivirals have not yet played a huge roll in the covid-19 pandemic, the clear need for a greater number of antivirals has spurred on research at a dramatic rate, and could potentially lead to the development of a wide variety of new antivirals, ready for the next pandemic.