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GS-441524: Introduction; Side effects and antiviral against ASFV

Dec 19，2023

Introduction of GS-441524

GS-441524, predominant metabolite of Remdesivir and superior to Remdesivir against Covid-19 , shows comparable efficacy in cell-based models of primary human lung and cat cells infected with coronavirus. GS-441524 could strongly inhibits feline infectious peritonitis virus (FIPV), with an EC50 of 0.78 μM. GS-441524 is also an effective antiviral against African swine fever virus (ASFV).

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Side effects

Animal studies have shown that GS-441524 may cause injection site reactions such as superficial lesions, open sores and scars in the treatment of feline infectious peritonitis (FIP). The ulcers healed within 2 weeks by clipping the surrounding hair and gently cleaning the wounds with cotton balls soaked in one part household hydrogen peroxide and two parts water twice daily. However, three cats had visible scars at the injection site.

No long-term abnormalities in complete blood count values were observed, and liver and kidney function and amylase/lipase levels remained normal during and after treatment. A gradual increase in blood urea nitrogen (BUN) may occur in rare cases.

Antiviral against ASFV

African swine fever virus (ASFV) is a highly contagious and lethal swine pathogen. GS-441524, a 1-cyano-substituted adenine C-nucleoside ribose analogue, inhibits viral RNA transcription by competing with natural nucleosides (ATP, TTP, CTP, and GTP) and effectively inhibits viral RNA-dependent RNA polymerase activity.

In this study, we confirmed that GS-441524 inhibits ASFV infection in porcine alveolar macrophages (PAMs) in a dose-dependent manner; GS-441524 significantly inhibited ASFV replication at different time points after ASFV infection, particularly at the early stages of viral replication. Notably, GS-441524 did not increase the levels of antiviral cytokines or ATP in PAMs. However, an increase in the concentration of natural ATP in PAMs promoted the replication of ASFV and attenuated the inhibitory effect of GS-441524 in a dose-dependent manner. Our results suggest that GS-441524 is an effective antiviral against ASFV.

References:

[1] ZHAO HUANG . GS-441524 inhibits African swine fever virus infection in vitro[J]. Antiviral research, 2021, 191: Article 105081. DOI:10.1016/j.antiviral.2021.105081.

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