This week, exciting news was released when Merck released the results of their clinical trial using a drug called molnupiravir, an antiviral targeted to reduce the severity of COVID-19. But what does the data actually show and what does it mean for COVID treatment?
Image credit: Christine Sandu on Unsplash
Antivirals are treatments for viral infections – unlike vaccines they do not aim to prevent the virus or spread, but to treat the infection once you already have it. Antivirals are a lot trickier to design than vaccines and are extremely specific to one virus. Whilst antibiotics (to treat bacterial infections) often work against a wide range of bacteria, antivirals only work against one virus – “one drug, one bug”. Antiviral development often lags behind vaccines and can take years to refine and approve.
There are a few choices to be made when designing an antiviral – which part of the virus should it target, and should it be custom made. Every virus is a compact container full of genes – some viruses only have two genes, whilst others can have over forty. Each gene is a possible target that antivirals could bind to and inhibit. The first step in designing an antiviral is picking a suitable gene to target – it should be a gene that does not mutate much (is conserved), and needs to be vital to the viral replication cycle (so that if we block it, the virus will die). More on antivirals and selecting target genes in a future post.
The Merck antiviral targets the viral polymerase (an enzyme vital to self-copying) within the virus. You can think of the polymerase as a photocopier, and each copy as a new virus ready to infect more cells. To stop the copies you could either prevent them from being made by turning off the electricity, jamming the paper, breaking the scanner screen or removing ink from the photocopier. Alternatively, you could let the copies be made, but make them bad quality by changing the colour scheme, changing the resolution or covering parts of the paper. This will result in copies still being produced, but none of them look as good as the original and may not even be recognisable. The Merck antiviral does the latter – it interferes with the copying process so that the new viruses have mutations and do not look like the original. This means they often cannot function properly and won’t be able to infect our cells, or if they do, they can’t successfully copy themselves later.
Molnupiravir interferes with the normal function of the viral polymerase enzyme and causes errors in the copied viruses.
The second choice to be made during antiviral development is whether to repurpose an existing drug or custom design a new one. Repurposing drugs is often a lot faster, because they have already been proven clinically safe, but they tend to be like trying to patch a circular hole with a square – they work well, but are not the perfect solution. Custom designing drugs will result in a perfect treatment, however the development process can take up to 15 years from beginning to approval.
The Merck antiviral is a repurposed drug, previously developed to treat influenza virus infection. Luckily, influenza works in a similar way to SARS-CoV-2 (polymerases are similar) meaning that the drug works “well enough” to be applied as a COVID treatment. The exact efficacy of molnupiravir is yet to be seen, however initial clinical trials show promising results; the drug decreased the amount of virus inside people and helped them clear the infection faster. If the drug continues to demonstrate favourable treatment outcomes during clinical trials, it could soon be approved for global treatment and will be the first COVID-specific treatment. It is unlikely that it will ever work as well as a drug custom designed for SARS-CoV-2, however anything that helps reduce the viral load in patients will be an incredible step forward for improving patient outcomes.
The clinical trials themselves are in early days and it is yet to be seen whether this specific drug will be approved for COVID-treatment, but regardless it is paving the way for the development of future virus-specific drugs to combat SARS-CoV-2.
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