The activity of (S)-1-[(3-hydroxy-2-phosphonyl methoxy) propyl] cytosine (HPMPC) against equine herpesvirus-1 (EHV-1) in cell cultures, mice and horses.
Abstract: The activity of the nucleotide analogue, (S)-1-[(3-hydroxy-2-phosphonyl methoxy) propyl] cytosine (HPMPC), against equine herpesvirus-1 (EHV-1) was tested in cell culture, mice and foals. The ED50 for plaque reduction was found to be 0.07 and 0.03 microgram/ml in RK-13 and EEL cells respectively. In mice, a single administration of HPMPC (20 mg/kg, s.c.) was very effective at reducing clinical signs and virus replication if given on the day before intranasal inoculation with EHV-1. Treatment on the day of infection or day 1 p.i. was less effective, but still significantly reduced clinical signs and virus titres in the target organs (lungs and nasal tissue). Furthermore, HPMPC was found to protect mice partially from an intracerebral inoculation with EHV-1. Experiments in the horse suggested that HPMPC was also very active against EHV-1 in the natural host. Thus a single administration of HPMPC at 20 mg/kg, s.c., on the day of infection, markedly reduced clinical signs and nasal excretion of virus following intranasal inoculation with EHV-1. HPMPC given as a divided dose of 1 mg/kg on day 0 and day 3 p.i. had no effect on clinical signs but did reduce nasal excretion of virus. The significance of these results is discussed.
Publication Date: 1992-09-01 PubMed ID: 1332605DOI: 10.1016/0166-3542(92)90081-fGoogle Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the effect of a nucleotide analogue, known as (S)-1-[(3-hydroxy-2-phosphonyl methoxy) propyl] cytosine (HPMPC), against equine herpesvirus-1 (EHV-1). The study finds that HPMPC demonstrates effectiveness in mitigating EHV-1 infection when applied in cell cultures, mice, and horses.
Effectiveness of HPMPC in Cell Cultures
- The study begins by examining the impact of HPMPC on EHV-1 when applied in cell cultures. Two types of cells were used for this purpose, named the RK-13 and EEL cells.
- It was observed that the half maximal effective concentration (ED50) was 0.07 and 0.03 micrograms per milliliter in the RK-13 and EEL cells respectively, suggesting substantial effectiveness against the virus.
Testing HPMPC in Mice
- The researchers then continued to test HPMPC in mice. A single dose of HPMPC at 20mg/kg was administered.
- The results indicate that when HPMPC is given before the EHV-1 inoculation, it was effective in significantly reducing the replication of the virus and the severity of the clinical signs of infection.
- Further, it was observed that administration of HPMPC on the day of, or even one day after infection, although less effective, managed to significantly decrease the severity of infection symptoms and the count of the virus in the targeted organs (mainly the lungs and nasal tissues).
- HPMPC has also been shown to provide partial protection against EHV-1 when the mice were inoculated intracerebrally with the virus.
Application of HPMPC in Horses
- The last part of the study moved on to test HPMPC in the natural host of the EHV-1 virus which is the horse.
- Similar to the results in mice, a single dose of HPMPC at 20mg/kg, s.c., managed to substantially decrease the severity of clinical signs as well as the nasal excretion of the virus when administered on the day of intranasal inoculation with EHV-1.
- It was also noted that a split dose of 1mg/kg of HPMPC administered on the day of infection and the third day post-infection did not have a significant effect on reducing the clinical signs. However, it did contribute to a reduction in the nasal excretion of the virus.
Conclusion
- In conclusion, the research paper provides significant evidence that HPMPC has an appreciable amount of effectiveness against EHV-1 and it can crucially decrease the level of infection when provided at the right time.
- It can serve as a starting point to future studies on the application of HPMPC or related nucleotide analogues against other infectious diseases prevalent in horses.
Cite This Article
APA
Gibson JS, Slater JD, Field HJ.
(1992).
The activity of (S)-1-[(3-hydroxy-2-phosphonyl methoxy) propyl] cytosine (HPMPC) against equine herpesvirus-1 (EHV-1) in cell cultures, mice and horses.
Antiviral Res, 19(3), 219-232.
https://doi.org/10.1016/0166-3542(92)90081-f Publication
Researcher Affiliations
- Department of Clinical Veterinary Medicine, Cambridge, UK.
MeSH Terms
- Administration, Intranasal
- Animals
- Antiviral Agents / pharmacology
- Antiviral Agents / therapeutic use
- Brain Diseases / drug therapy
- Brain Diseases / veterinary
- Cidofovir
- Cytosine / analogs & derivatives
- Cytosine / pharmacology
- Cytosine / therapeutic use
- Drug Administration Schedule
- Female
- Herpesviridae Infections / drug therapy
- Herpesviridae Infections / veterinary
- Herpesvirus 1, Equid / drug effects
- Herpesvirus 1, Equid / isolation & purification
- Horse Diseases / drug therapy
- Horses
- Mice
- Mice, Inbred BALB C
- Organophosphonates
- Organophosphorus Compounds / pharmacology
- Organophosphorus Compounds / therapeutic use
Citations
This article has been cited 4 times.- Tempesta M, Crescenzo G, Camero M, Bellacicco AL, Tarsitano E, Decaro N, Neyts J, Martella V, Buonavoglia C. Assessing the efficacy of cidofovir against herpesvirus-induced genital lesions in goats using different therapeutic regimens. Antimicrob Agents Chemother 2008 Nov;52(11):4064-8.
- Awan AR, Field HJ. Effects of phosphonylmethoxyalkyl derivatives studied with a murine model for abortion induced by equine herpesvirus 1. Antimicrob Agents Chemother 1993 Nov;37(11):2478-82.
- Goehring L, Dorman DC, Osterrieder K, Burgess BA, Dougherty K, Gross P, Neinast C, Pusterla N, Soboll-Hussey G, Lunn DP. Pharmacologic interventions for the treatment of equine herpesvirus-1 in domesticated horses: A systematic review. J Vet Intern Med 2024 May-Jun;38(3):1892-1905.
- Pusterla N, Dorman DC, Burgess BA, Goehring L, Gross M, Osterrieder K, Soboll Hussey G, Lunn DP. Viremia and nasal shedding for the diagnosis of equine herpesvirus-1 infection in domesticated horses. J Vet Intern Med 2024 May-Jun;38(3):1765-1791.
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