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Possible Antiviral Activity of 5-Aminolevulinic Acid in Feline Infectious Peritonitis Virus (Feline Coronavirus) Infection

Takano T, Satoh K, Doki T. Possible Antiviral Activity of 5-Aminolevulinic Acid in Feline Infectious Peritonitis Virus (Feline Coronavirus) Infection. Front Vet Sci. 2021;8. doi:10.3389/fvets.2021.647189

Feline Infectious Peritonitis (FIP) is a life-threatening disease of cats that is caused by an aberrant immune response to a mutated form of feline enteric coronavirus. FIP has previously been discussed on this blog at length, especially in relation to recent changes in the diagnosis and treatment of this serious disease. While recent breakthroughs in therapy have occurred that allow for treatment of a previously fatal condition, these therapies are expensive, difficult to attain, dubiously legal, and not 100% effective. As such, research into novel treatment options is important in order to provide new and accessible options for therapy. 5-aminolevulinic acid (5-ALA) is a low-molecular-weight amino acid that is widely available and synthesized for application in medical and agricultural fields. It has been shown to have antimalarial and anti neoplastic effects in some species.
The purpose of this study was to determine if 5-ALA has antiviral effects against feline coronavirus in vitro.
Cultured feline cells (fetal cells, primary macrophages, and alveolar macrophages) were grown in a laboratory. 5-ALA and sodium ferrous citrate (SFC) were used as test agents. SFC was used as a vehicle control. Both type I and type II feline coronavirus strains were tested; the type I strain was a laboratory adapted FIPV strain while the type II was not.
5-ALA was assessed for cytotoxicity to feline cells by plating in a 96-well plate, treating with various dilutions of 5-ALA, and the cells assessed for viability and the 50% cytotoxicity concentration determined. Cells were then treated with 5-ALA or SFC at a range of concentrations, followed by incubation with the virus. Virus titres were then determined after 48 hours and the EC50 (concentration that decreased viral titer by 50%) determined.
More than 75% of cells survived exposure to a 1000uM concentration of 5-ALA, which was the maximum concentration used in this study. As such the 50% cytotoxicity concentration was not determined. The SFC control showed no cytotoxicity.
The production of type I and type II coronavirus was inhibited by 250uM and 500uM of 5-ALA, respectively in fetal cells. Virus production of type I FIPV was inhibited in macrophages by 250mM 5-ALA.
Based on this data, the authors concluded that 5-ALA is able to inhibit FIPV replication in an in-vitro model. They also concluded that it was able to inhibit TNF-alpha production, something that is not apparently supported by this study. They also concluded that, since anticoronaviral activity was not seen in all macrophage cultures, monotherapy with 5-ALA should likely not be considered.
A major limitation to this study is the preliminary and in vitro nature. While this type of study is essential to the development of novel drugs, it is important to recall that in vitro efficacy does not always translate to in vivo efficacy or safety, and extensive research is needed to confirm its practical use. The study also only tested the effects of 5-ALA on two strains of coronavirus, only one of which was a FIPV strain.
This study provides evidence that a novel therapy may have efficacy against FIP, and suggests that further research into 5-ALA as an anticoronaviral drug should be pursued.

See Also:
1. Motokawa K, Hohdatsu T, Aizawa C, Koyama H, Hashimoto H. Molecular cloning and sequence determination of the peplomer protein gene of feline infectious peritonitis virus type I.Arch Virol. (1995) 140:469–80
2. Chang HW, Egberink HF, Halpin R, Spiro DJ, Rottier PJ. Spike protein fusion peptide and feline coronavirus virulence. Emerg Infect Dis. (2012)18:1089
3. Pedersen NC, Perron M, Bannasch M, Montgomery E, Murakami E, Liepnieks M, et al. Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis. J. Fel Med Surg. (2019). 21:271-81

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