Products Cited in Publications Worldwide Are unlicensed feline coronavirus antiviral compounds GS-441524 and GC376 what they claim to be? A qualitative and quantitative analysis.

Are unlicensed feline coronavirus antiviral compounds GS-441524 and GC376 what they claim to be? A qualitative and quantitative analysis.

Aidan J. Mulligan; Megan E. Browning

DOI:

Abstract

Background: Feline Infectious peritonitis (FlP) is a disease caused by feline coronavirus. FlP is100% fatal and was considered untreatable until recently. Although there is no FDA-approved treatment for FlP, experimental drugs, GS-441524 (the primary metabolite ofremdesivir), GC376 (a viral protease inhibitor), and Molnupiravir have been foundeffective in treating this otherwise fatal disease. Because of the severity of FlP and lackof approved treatments, these drugs are sometimes used off-label to treat this diseaseThese drugs can be obtained through crowdsource online social media groups. Methods: We tested 28 vials from 10 brands of GS-441524 and 5 vials from one brand of GC376We compared the GS-441524 to a control standard from Ambeed and the GC376 to astandard from Cayman Chemical. We recorded physical appearance, pH, absorbance.high-performance liquid chromatography retention times, and thin-layer chromatographyretention factors for all of them. Some were also used for nuclear magnetic resonanceand mass spectrometric analysis. Objectives: These medications are unregulated, and therefore come with potential risks for animalsbeing treated. This study set out to determine the purity of various batches of thesedrugs from several companies, characterizing them, and noting any impurities or other unusual characteristics. We also developed a method to qualitatively assess the primancomponents prior to administration. Results: Most of the GS-441524 samples tested were similar in purity and composition, bothbetween batches and between brands. Most of the brands tested had concentrations of GS-41524 similar to the concentration advertised. 3 of the 17 types of vials tested hadconcentrations over 10% above advertised, and one was over 20% higher thanadvertised. One batch, known to have significant quality concems based on the lack ofefficacy in animals treated, had a concentration almost 50% below advertised. We alsctested 5 vials of GC376 and found 1/5 vials contained GS-441524 rather than GC376 and the other 4/5 vials contained Molnupiravir Conclusions: Most of the vials tested contained the advertised drug at the labeled concentration.Some of the GS-441524 vials were 10-25% more concentrated than advertised butgiven the low toxicity this is probably not of great concern. However, one batch hadapproximately half the expected concentration, which explains the reported lack ofefficacy. None of the GC376 vials tested contained GC376. GC376 is used in cats thatare unresponsive to GS-441524, and use of the wrong antiviral can cause serious sideeffects. in addition, we provide suggested methods for determining the purity of newbatches of these compounds and distinguishing one drug from the other.

Keywords

Feline coronavirus ; Feline infectious peritonitis ; GS-441524 ; GC376 ; Off-label Use ; Molnupiravir

Purchased from AmBeed

GS-441524

A11592461191237-69-099%

GS-441524

320.0/10g

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