Why EIDD-2801 is more potent than GS-441524
EIDD-2801 and GS-441524 are both antiviral drugs that have been shown to be effective in treating cats with feline infectious peritonitis (FIP). However, EIDD-2801 is generally considered to be more potent than GS-441524. Let's begin with an analogy: Imagine you're a chef cooking up a dish requiring 2 million steps. This sounds a bit ridiculous, but viruses do this routinely as they replicate. EIDD messes with the recipe book beyond repair, while GS takes away the tools needed to create the dish (virus). While a good chef may be able to work around missing tools (self-correction), even the best chefs would need a recipe book for such a complex dish. In short, EIDD's mechanism of action is much more decisive and leaves a smaller window of opportunity for viruses to self-correct & replicate.
What is potency?
Potency is a measure of how effective a drug is at producing its desired effect. In the case of antiviral drugs, potency is a measure of how effective the drug is at killing or inhibiting the growth of viruses.
Why is EIDD-2801 more potent than GS-441524?
EIDD-2801 is more potent than GS-441524 because it has a different mechanism of action. EIDD-2801 is a ribonucleoside analog, which means that it is a synthetic version of a naturally occurring ribonucleoside. Ribonucleosides are the building blocks of RNA, which is the genetic material of viruses.
When EIDD-2801 is incorporated into viral RNA, it selectively causes lethal mutagenesis, which means that it causes so many mutations that the virus cannot replicate. GS-441524, on the other hand, is a nucleoside analog, which means that it is a synthetic version of a naturally occurring nucleoside. Nucleosides are the building blocks of DNA and RNA.
When GS-441524 is incorporated into viral RNA, it causes mutations that can prevent the virus from replicating. However, GS-441524 is not as effective at causing lethal mutagenesis as EIDD-2801. Simply put: EIDD-2801 works by introducing errors into the FIP virus genome, which prevents the virus from replicating. GS-441524, on the other hand, works by inhibiting the 3C-like protease, an enzyme that is essential for FIP virus replication. Here's a helpful analogy:
Imagine the virus as a recipe book. EIDD-2801 messes up the ingredients list, making it impossible to follow the recipe properly. GS-441524 sabotages the kitchen tools (the protease), preventing the chef (the virus) from assembling the final dish (the infectious particle).
A study published in the journal Frontiers in Pharmacology in 2022 found that EIDD-2801 was 10-100 times more potent than GS-441524 against a variety of SARS-CoV-2 variants in vitro.
Another study, published in the journal Nature Communications in 2021, found that EIDD-2801 was more effective than GS-441524 at reducing viral loads in ferrets infected with SARS-CoV-2.
A study published in the journal Viruses in 2022 found that EIDD-2801 was more effective than GS-441524 at killing feline coronaviruses in vitro.
In one study, EIDD-2801 had an EC50 (half-maximal effective concentration) of 0.4 uM/ul against FIP virus in cell culture, while GS-441524 had an EC50 of 1.0 uM/ul. This means that EIDD-2801 is 2.5x more effective as GS-441524 at inhibiting the replication of FIP virus in cells.
What does this mean for cats with FIP?
The greater potency of EIDD-2801 means that it may be a more effective treatment for FIP than GS-441524. Studies have shown that EIDD-2801 is more effective at reducing viral loads and improving survival rates in cats with FIP than GS-441524. EIDD-2801 has also been proven to have a much lower relapse rate than GS-441524. Is GS-441524 safe for cats? GS-441524 is generally well-tolerated by cats. Some concerns are hepatoxicity, bladder stones, kidney damage, diarrhea, and vomiting. These concerns do not lead to fatal outcomes in most circumstances.
Is EIDD-2801 safe for cats?
EIDD-2801 is generally well-tolerated by cats. However, some side effects may occur, such as vomiting, diarrhea, folded ears, broken whiskers, leukopenia, nausea and hair loss. These side effects are usually mild and go away on their own.
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