High Quality 99% GS-441524 Powder CAS 1191237-69-0

GS-441524 More Info

GS-441524 is a nucleoside analogue antiviral drug, primarily recognized as the main metabolite of the prodrug remdesivir. It has garnered attention for its effectiveness against various viral infections, particularly in treating feline infectious peritonitis (FIP) in cats and showing potential against SARS-CoV-2.

Mechanism of Action

GS-441524 functions as a nucleoside analogue, requiring intracellular phosphorylation to become active. It is converted into its triphosphate form, which then acts as a false substrate for viral RNA-dependent RNA polymerase (RdRp). This process leads to chain termination during viral RNA synthesis, effectively halting viral replication.

Applications

GS-441524 is a nucleoside analogue with several notable applications, primarily in the treatment of viral infections. Here’s a detailed overview of its applications:
1. Treatment of Feline Infectious Peritonitis (FIP)
Standard Treatment: GS-441524 is now considered the standard treatment for FIP, a severe and often fatal disease caused by feline coronaviruses (FCoV) that affects domestic cats. Historically, FIP was nearly always fatal until the introduction of GS-441524, which has shown significant efficacy in clinical settings.
Mechanism: It acts as a nucleoside analogue, incorporating into the viral RNA during replication, thereby inhibiting viral replication and leading to chain termination.
Clinical Efficacy: Studies have demonstrated that GS-441524 effectively reduces the viral load in infected cats, with many showing complete recovery after treatment.
2. Potential Use Against Human Coronaviruses
SARS-CoV-2: GS-441524 has been shown to inhibit SARS-CoV-2 in vitro, with studies indicating it may be more effective than remdesivir against this virus. The compound has demonstrated low half-maximal inhibitory concentration (IC50) values against SARS-CoV-2, suggesting strong antiviral activity.
Other Coronaviruses: It also exhibits inhibitory effects on other coronaviruses such as SARS-CoV and MERS-CoV, which could position it as a potential therapeutic option for these diseases.
3. Research Applications
Understanding Viral Mechanisms: Ongoing research is investigating GS-441524's dual functions—acting as both a nucleoside analogue and a potential inhibitor of viral macrodomain enzymes, which play roles in counteracting host antiviral defenses. This dual action may provide insights into developing new antiviral strategies.
Resistance Studies: Research is also focusing on the potential emergence of resistance to GS-441524 among FCoV strains, which is critical for ensuring long-term efficacy and developing new antiviral agents targeting FCoV.
4. Other Viral Infections
Broad-Spectrum Antiviral Activity: Beyond coronaviruses, GS-441524 has shown promise against various RNA viruses in preliminary studies. Its efficacy against viruses such as Ebola and respiratory syncytial virus (RSV) has been noted, indicating its potential as a broad-spectrum antiviral agent.

Routes of Administration

GS-441524 is primarily administered via injection. During clinical trials, it was prepared in a solution comprising:

5% ethanol
30% propylene glycol
45% PEG 400 (polyethylene glycol)
20% water adjusted to pH 1.5

This mixture was dissolved and stored under refrigeration for use within a few weeks.