Feline medicine and therapeutics
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Based on experience with other viral protease inhibitors, similar drugs are now being developed against the main protease 3CL encoded by both coronaviruses and noroviruses Kim et al. Many of the structural proteins of coronavirus are first transcribed from mRNA as polyproteins which are cleaved by proteases into their constituent parts.
Although cellular proteases have been assumed to play a major role in cleaving FIPV polyproteins, preliminary in vitro tests show 3CL protease inhibitors are effective in inhibiting FIPV replication at levels that are not toxic to cells Kim et al. The drug chloroquine, which is used to treat malaria, has been shown to inhibit FIPV replication in vitro and has anti-inflammatory properties Takano et al. It was then. Cyclosporine A has also been shown to possess anti-coronavirus activity. Pfefferle et al. This confirms a role for cellular immunophilins cyclophilins in coronavirus replication.
The authors postulated that non-immunosuppressive derivatives of cyclosporine A might not only serve as broad-spectrum inhibitors of emerging human coronaviruses, but also of the more ubiquitous coronavirus pathogens of humans and livestock. The ability of cyclosporine A to inhibit feline coronavirus replication in cell culture has been confirmed, but it has not been tested in vivo Tanaka et al. The problem with antiviral agents such as chloroquine and cyclosporine is that they work through pathways common to cellular and viral activities.
Coronaviruses usurp normal cellular pathways to facilitate their own replication and the anti-viral effects of compounds such as chloroquine and cyclosporine cannot be separated from their other effects on cells and, therefore, the host. For example, the antiviral activity of chloroquine in vivo was inferior to in vitro activity and there were toxic effects in the host Takano et al.
Hseih et al.
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Galanthus nivalis. When the level of virus infection was increased to mimic that of target. However, when the. No further reports of these drugs in cats with FIP have been. It is doubtful whether a natural agglutinin would have any anti-viral effect in vivo,.
Under these conditions, the susceptibility of the cells to virus infection was. This study indicated. However, it must.
Feline Medicine and Therapeutics, 3rd Edition
Liu et al. The peptides inhibited virus replication by blocking the intercalation of the HR1 and HR2 regions, which is necessary for the activation of S protein-mediated fusion. A synergistic effect was found with human interferon-a. The authors concluded that this peptide could be a valuable addition to current FIP prevention methods, but it should be remembered that using such peptides in vivo is quite different to using them in vitro.
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A number of drugs have both anti-inflammatory and immunosuppressive activity. Prednisolone and alkylating drugs such as cyclophosphamide have been used to reduce clinical signs in cats with FIP, but there is no evidence that they altered the disease outcome. Rather than using this less specific therapeutic approach, attempts have been made to inhibit specific cytokines deemed to be important in the pathogenesis of FIP.
One of the most popular of these drugs is pentoxyfilline Fischer et al. Pentoxyfylline was widely used in FIP because of its use in controlling vasculitis in humans, vasculitis being an important component of the pathophysiology of FIP. A study of 23 cats with proven FIP failed to detect an effect of pentoxyfylline on the survival time, the quality of life or any FIP-associated clinical or laboratory parameters Fischer et al. The current rush to use this biologic agent was based on a study of three cats, one of which. However, all three. The authors also failed to consider.
Therefore, there is no evidence. Furthermore, these compounds. The dosage regimen for such drugs is often uncertain and frequently based more on limiting costs to the owners by administering small doses or treating less frequently. This lack of information is in itself evidence of the quality of pre-testing. None of these immunostimulants have been subjected to vigorous pharmacokinetic and bioactivity studies, although all appear to be safe. In the absence of adequate pretesting, it is important to do valid clinical testing prior to recommending these agents for general use.
Proper clinical testing requires the use of a placebo control, randomization, double blinding, sufficient case numbers for statistical validity and accurate determination of disease status. FIP has been well documented in virtually every species of Felidae.
FIP of domestic cats and cheetahs has been historically intertwined Pearks et al. Initial studies of genetic diversity among cheetahs concluded that they were extremely inbred as a species, to the point of accepting skin grafts from each other, and that this inbreeding was a result of an extreme bottleneck that occurred some 12, years earlier. If correct, this degree of inbreeding would have made the species highly vulnerable to the introduction of a novel and highly fatal pathogen. This paradigm was thought to have been realized when a fatal epizootic of what appeared to be FIP caused by feline coronavirus occurred among captive cheetahs at Winston Safari park in Oregon, USA, in the early s.
The outbreak started with two confirmed FIP deaths among. Ninety percent of the 60 Cheetahs in the park became ill over the. This was later found to be incorrect. Castro-Prieto et al. Cheetahs in the wild were found to have an extremely low rate of. However, almost half of healthy captive cheetahs shed feline coronavirus. Terada et al. What is certain is that.
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The fact that ferret coronavirus exists in several genetic forms indicates that coronaviruses. Has a new ferret coronavirus evolved that is more likely. As ferrets have become more popular as pets, do they. Coronavirus antibody titers can be misleading in the range of to , but. Many of these therapies are expensive and come with a high emotional burden. It is.
The most promising therapies will probably involve drugs that specifically target viral proteins important in viral replication. Coronaviruses have large genomes with many potential target genes and hopefully safe and effective antiviral drugs will be developed. It is anticipated that such drugs might be developed as offshoots of research investigating emerging and highly fatal coronavirus infections of humans. The author has no financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of this paper.
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Addie, D. Quarantine protects Falkland Islands Malvinas cats from feline coronavirus infection. Journal of Feline Medicine and Surgery 14, Feline infectious peritonitis. ABCD guidelines on prevention and management. Journal of Feline Medicine and Surgery 11, Amer, A. Isolation and molecular characterization of type I and type II feline coronavirus in Malaysia. Virology Journal 9, An, D. Prevalence of Korean cats with natural feline coronavirus infections. Virology Journal 8, Bauer, B. Positive immunostaining for feline infectious peritonitis FIP in a Sphinx cat with cutaneous lesions and bilateral panuveitis.
Veterinary Ophthalmology 16 Suppl. Cheetah paradigm revisited: MHC diversity in. Decreased sialylation. Feline infectious peritonitis:. Spike protein fusion. Papular cutaneous lesions in.