Remdesivir and GS-441524 are both antiviral drugs, and they share some similarities, but they also have important differences. Here's an overview of these differences:
Origin and Development:
Remdesivir: Remdesivir was developed by Gilead Sciences as a broad-spectrum antiviral medication. It was originally developed for the treatment of Ebola virus disease and later repurposed for other viral infections, including SARS-CoV-2 (the virus that causes COVID-19).
GS-441524: GS-441524 is a molecule that is structurally very similar to remdesivir. It is not a pharmaceutical drug but a metabolite or derivative of remdesivir. GS-441524 has been studied primarily in the context of veterinary medicine and for its potential use against feline infectious peritonitis (FIP), a coronavirus in cats.
Clinical Use:
Remdesivir: Remdesivir has been authorized or approved for emergency use in several countries for the treatment of COVID-19 in hospitalized patients. It has been used as a therapeutic option for individuals with severe disease.
GS-441524: GS-441524 is not approved for human use. It has been studied primarily in veterinary medicine, particularly for treating FIP in cats. It is not an authorized or recommended treatment for COVID-19 in humans.
Structure:
Remdesivir: Remdesivir is a prodrug, which means that it must be metabolized in the body to its active form, GS-441524, to exert its antiviral effects. It contains a phosphoramidate moiety that gets cleaved in the body, releasing GS-441524.
GS-441524: GS-441524 is the active form of remdesivir. It lacks the phosphoramidate group found in remdesivir, which is responsible for its prodrug nature. GS-441524 is the molecule that directly inhibits viral RNA synthesis.
Legal and Regulatory Status:
Remdesivir: Remdesivir has received emergency use authorization and full approval for use in humans by regulatory agencies in various countries, including the FDA in the United States.
GS-441524: GS-441524 is not approved for human use and is primarily a research compound. It has been used experimentally in veterinary medicine, particularly for FIP in cats.
Many veterinarian around the world decided to use Remdesivir for FIP treatment despite the fact that it has not been clinically studied or proved for such cases. Now let's dive deep into the use of both medications for cat FIP treatment in particular:
FIP Dosage Required Dosage:
The molecular weight of Remdesivir is 603 g/mol, whereas the molecular weight of GS-441524 is 291 g/mol. While there is a difference in molecular weight between these compounds, it's important to emphasize that determining the appropriate dosage for a medication involves more complex factors than just molecular weight. However, this info, in result, shows that the cat needs double the dose when treated with Remdesivir compared to GS441524 dose.
Preparation and Storage of Treatment:
To administer Remdesivir for treating FIP, it should be meticulously prepared using saline solution, subsequently stored in a refrigerator, and must be utilized within a span of 5 days. In contrast, GS441524 injection vials come readily prepared for use and can be directly administered through subcutaneous injection. When stored at ambient temperatures, shielded from direct sunlight, the shelf life of GS441524 extends up to 2 years.
GS441524 is also available in tablet form, which can be given orally to those FIP cats which eat and defecate normally on their own with no digestive system issues.
Potential for Toxicity:
When considering the treatment of Feline Infectious Peritonitis (FIP) in cats, clinical trials involving GS441524 have demonstrated a notably favorable safety profile. After an 84-day treatment period, there were no reported adverse side effects. Dr. Pedersen's assessment highlighted the remarkable safety record of GS441524, noting the absence of systemic signs of toxicity even at subcutaneous doses up to 10 mg/kg, which were used to address neurological manifestations of FIP. Notably, even at these higher doses, GS441524 treatment led to long-term resolution of neurological FIP with minimal dose-related toxicities.
In contrast, the study of Remdesivir in FIP treatment is quite limited, and it is important to acknowledge that mild indications of liver and kidney toxicity have been observed in its use for COVID-19 treatment in humans. Adverse events associated with Remdesivir therapy encompass mild to moderate symptoms such as nausea, vomiting, headaches, fatigue, renal dysfunction, serum aminotransferase elevations, and rashes. Additionally, there have been rare reports of hypersensitivity reactions, acute renal dysfunction, and liver injury.
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