Why is GS-441524 the most promising antiviral drug?

According to some recent biological studies, GS-441524 is one of the most promising antiviral drugs at this stage. It is well known that wherever there is life, there is a virus. Viruses can infect all living organisms with cellular structure. To fight against viruses, scientists have developed many antiviral drugs. Just like antibiotics for bacterial infections, specific antiviral drugs work only on specific viruses. Antiviral drugs have also been a very popular research topic, and various antiviral drugs are emerging, so what are the characteristics of GS-441524, a new drug recently developed by a biological company, that allow us to judge it as the most promising antiviral drug?

What is GS-441524?

GS-441524 is a nucleoside analogue antiviral drug developed by Gilead Sciences. It is the primary plasma metabolite of the antiviral prodrug remdesivir and has a half-life of approximately 24 hours in human patients. upon entry into cells, GS-441524 is metabolized to an active triphosphate that induces RNA strand termination and inhibits viral polymerase. the GS-441524 nucleoside is phosphorylated by nucleoside kinase and then rephosphorylated by nucleoside-diphosphate kinase (NDK) to the active nucleoside triphosphate form. The triphosphate of GS-441524, GS-443902, is also a biologically active antiviral agent produced by remdesivir, but the biochemical mechanism of its production differs from that of the latter. It is active against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome CoV (SARS-CoV) in infected primary human airway epithelial (HAE) cells. In addition to this, GS-441524 was also found to be effective in vitro against the feline coronavirus strain that causes feline infectious peritonitis (FIP) in organisms.


Research directions for GS-441524

It is because studies have indicated that GS-441524 is effective against the strain of feline coronavirus that causes feline infectious peritonitis (FIP). Therefore, many veterinarians have begun to investigate whether this drug can be used in more complex FIP, such as fIP with multiple systemic or neurological involvement, and it has been shown to be very effective. GS-441524 This drug is often used to treat household pet cats.

GS-441524 has also been found to be useful against SARS-CoV-2 virus in biological experiments. GS-441524 is easier to synthesize than remdesivir, and it is less toxic to the kidney and liver.

It is because of these advantages of GS-441524, an antiviral drug, that our laboratory has also purchased a batch of research-grade GS-441524 from BenchChem, a chemical supplier in California, to study its efficacy principles. In our experiments, we found that GS-441524 is triphosphorylated intracellularly to produce an active 1′-cyano-substituted adenosine triphosphate analogue, which competes with endogenous NTPs by incorporation into nascent viral RNA transcripts and triggering delayed strand termination by RNA-dependent RNA polymerase, directly interrupting viral RNA replication.

Because GS-441524 is the main metabolite of remdesivir, many experiments will now also revolve around his comparison with remdesivir, which is already a very mature product, but GS-441524 still has a lot to be discovered by us. We also hope that after the initial understanding of the principle of GS-441524 as a drug, we can make more discoveries about its use scenarios.

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