Topic:Antiviral
Antiviral agents in horses refer to substances used to prevent or treat viral infections in equine species. These agents can target various stages of the viral life cycle, aiming to reduce viral replication and alleviate clinical symptoms. Antiviral treatments in horses may include nucleoside analogs, neuraminidase inhibitors, and other compounds that interfere with viral entry or replication. The effectiveness and safety of these agents can vary depending on the specific virus and the individual horse. This page compiles peer-reviewed research studies and scholarly articles that explore the mechanisms, efficacy, and clinical applications of antiviral agents in equine medicine.
Evaluation of immune globulin and recombinant interferon-alpha2b for treatment of experimental Ebola virus infections. A passive immunization strategy for treating Ebola virus infections was evaluated using BALB/ c mice, strain 13 guinea pigs, and cynomolgus monkeys. Guinea pigs were completely protected by injection of hyperimmune equine IgG when treatment was initiated early but not after viremia had developed. In contrast, mice were incompletely protected even when treatment was initiated on day 0, the day of virus inoculation. In monkeys treated with one dose of IgG on day 0, onset of illness and viremia was delayed, but all treated animals died. A second dose of IgG on day 5 had no additional beneficial e...
Equinins in equine neutrophils: quantification in tracheobronchial secretions as an aid in the diagnosis of chronic pulmonary disease. Equinins are a closely related group of proteins found in equine neutrophil granules. They demonstrate proteinase inhibiting activity restricted to microbial proteinase K and subtilisin, and they also possess antibacterial and antiviral properties. Antiproteinase K activity was measured in tracheobronchial secretions (TBS) of horses with mild (n = 15), moderate (n = 30) and severe (n = 16) chronic pulmonary disease, to determine its usefulness as an indicator of severity of disease and to measure neutrophil content. Determination of proteinase K inhibiting activity was based on a colorimetric ...
Neonatal equine herpesvirus type 1 infection on a thoroughbred breeding farm. Of 17 foals born on a Thoroughbred breeding farm between March and April 1995, infection with equine herpesvirus type 1 (EHV-1) was associated with neonatal morbidity in 5 foals, 3 of which died or were euthanized. Morbidity and mortality were associated with pulmonary inflammation, and EHV-1 was identified in the lungs of the 3 foals that died. All neonatal EHV-1 infections occurred in foals of mares housed in the same pasture and barn. No other clinical manifestations of EHV-1 infection (e.g., abortion, neurologic disease, or respiratory disease) occurred during this outbreak. Three foals we...
A novel family of viral death effector domain-containing molecules that inhibit both CD-95- and tumor necrosis factor receptor-1-induced apoptosis. Molluscum contagiosum virus proteins MC159 and MC160 and the equine herpesvirus 2 protein E8 share substantial homology to the death effector domain present in the adaptor molecule Fas-associated death domain protein (FADD) and the initiating death protease FADD-like interleukin-1beta-converting enzyme (FLICE) (caspase-8). FADD and FLICE participate in generating the death signal from both tumor necrosis factor receptor-1 (TNFR-1) and the CD-95 receptor. The flow of death signals from TNFR-1 occurs through the adaptor molecule tumor necrosis factor receptor-associated death domain protein (TRA...
Amantadine and equine influenza: pharmacology, pharmacokinetics and neurological effects in the horse. Amantadine is an antiviral agent effective against influenza A viruses. We investigated 1) the antiviral efficacy, 2) analytical detection, 3) bioavailability and disposition, 4) pharmacokinetic modelling and 5) adverse reactions of amantadine in the horse. In vitro, amantadine and its derivative rimantadine suppressed the replication of recent isolates of equine-2 influenza virus with effective doses (EDs) of less than 30 ng/ml. Rimantadine was more effective than amantadine against most viral isolates; we suggest a minimum plasma concentration of 300 ng/ml of amantadine for therapeutic effic...
Amantadine in man and horse–can we learn from each other? The research examines the impact of administering amantadine to horses and humans to combat influenza A, speculating on potential benefits of dual-field research between human and animal health. The study […]
Clinical application of interferons in large animal medicine. Interferons are efficacious therapeutic agents for treatment of several clinically important diseases in cattle and horses. In some instances, the therapeutic goal of IFN administration is prevention or clinical cure of acute viral infections. On the other hand, IFN may serve as adjunctive treatment to diminish clinical manifestations of disease and improve the quality of life. Oral administration of IFN alpha appears to be a safe and convenient route of administration, and the therapeutic benefit likely develops via unique mechanisms involving oropharyngeal-associated lymphoid tissue for diss...
Equine arteritis virus subgenomic RNA transcription: UV inactivation and translation inhibition studies. The expression of the genetic information of equine arteritis virus (EAV), an arterivirus, involves the synthesis of six subgenomic (sg) mRNAs. These are 5' and 3' coterminal since they are composed of a leader and a body sequence, which are identical to the 5' and 3' ends of the genome, respectively. Previously, it has been suggested that cis-splicing of a genome-length precursor RNA is involved in their synthesis. This was reevaluated in a comparative analysis of the sg RNA synthesis of EAV, the coronavirus mouse hepatitis virus (MHV), and the alphavirus Sindbis virus. UV transcription mappi...
Experimental treatment of equine sarcoid using a xanthate compound and recombinant human tumour necrosis factor alpha. A xanthate compound with antiviral and antitumoural activities, tricyclodecan-9-yl-xanthogenate (D609) in combination with the potassium salt of the lauric acid (KC12) and, in a further investigation, the above-mentioned substances together with recombinant human TNF alpha (rh-TNF alpha), were tested on equine sarcoid tumours for therapeutic efficacy. A pilot investigation on 5 healthy horses showed that the compounds were well-tolerated; apart from a local, temporary oedema at the injection site, no other clinical symptoms were observed after subcutaneous administration of volumes from 0.1 to...
Kinetics of inhibition of replication of vesicular stomatitis virus in blood mononuclear cells of horses after in vitro and in vivo treatment with recombinant equine interferon-beta 1. Recombinant equine interferon-beta 1 (reqIFN-beta 1) induces an antiviral state in blood mononuclear cells (BMC) of horses. Maximal protection against replication of vesicular stomatitis virus is achieved 6 hours after treatment with IFN in vitro and in vivo. Duration of the protective effect depends on the dose of IFN in vitro and in vivo. Availability of reqIFN-beta 1 in cultures of BMC for up to 48 hours does not prolong the antiviral state. The protective effect on BMC after treatment with IFN has similar duration in vivo and in vitro. Monitoring of the effect of IFN in vivo is, thus, simp...
Nucleotide sequence of the equine interferon gamma cDNA. Interferon gamma, a cytokine produced by T-lymphocytes and natural killer cells, plays a central role in the modulation of the immune response, and its antiviral and antitumourigenic properties have made it a potential candidate for use in immunoprophylactic and therapeutic regimes. We have cloned the equine IFN gamma cDNA to facilitate production of this cytokine for clinical evaluation in the horse. The predicted equine IFN gamma amino acid sequence is 67% identical to that of the human equivalent and 78% to the bovine equivalent.
Animal immunodeficiency viruses. Feline immunodeficiency virus (FIV) has morphological, physical and biochemical characteristics similar to human immunodeficiency virus (HIV), the cause of AIDS in man. However, it is antigenically and genetically distinct from HIV; an antigenic relatedness with equine infectious anaemia virus has been demonstrated. FIV has been molecularly cloned and sequenced. Diagnostic tests are commercially available and attempts at preparing inactivated, subunit and molecularly engineered vaccines are being made in different laboratories. During FIV infection a transient primary illness can be recognized...
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. 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 sign...
Monitoring of effects induced by recombinant equine interferon-beta 1 in whole blood and separated fractions of peripheral blood of horses. Interferon is known to induce antiviral mechanisms and to exert immunoregulatory capacities on various cell types. The antiviral capacity of recombinant equine interferon-beta 1 (rEqIFN-beta 1) is most sensitively monitored by indirect quantitation of multiplication of vesicular stomatitis virus (VSV) in blood cells of horses. As few as 0.5 pg rEqIFN-beta 1/ml can be assessed by means of 90% reduction of VSV-replication in whole blood (w.b.) as well as in isolated mononuclear blood cells (MNC) in spite of individual variations. The immunoregulatory influence of 20-50 pg rEqIFN-beta 1/ml is suf...
Isolation of equine herpesvirus-1 mutants in the presence of (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine: demonstration of resistance in vitro and in vivo. The compound (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) had been previously shown to be highly effective in treatment of EHV-1 in a murine model for the equine disease. This paper describes the isolation of a series of mutants resistant to the drug. Resistance was demonstrated in cell culture and one mutant was tested in a murine model. The resistant mutant was pathogenic for mice; infectious virus was recovered from respiratory tissues and blood at levels similar to the parental virus. However, the mutant showed a significant degree of resistance in vivo, thus proving the viru...
Neutralization of HIV-1: a paradox of humoral proportions. The production of immunoglobulin capable of neutralizing the infectivity of a virus represents one of the most remarkable molecular accomplishments of the host's available immune defenses. It should be no surprise that a virus that has existed in the parenchyma of the immune system has evolved as an equally dynamic molecule (i.e., viral envelope) for survival. Neutralizing immunoglobulin (Ig) can best serve the host under conditions where the invading pathogen requires a well-defined cell-free state for establishing an infection or transmission. Evidence for a controlling and therefore protect...
Investigation of antigenic structure of attenuated and virulent Venezuelan equine encephalomyelitis virus by means of monoclonal antibodies. A comparative study of the antigenic structure of virulent strains and attenuated vaccine strains of Venezuelan equine encephalomyelitis virus (VEEV) by means of monoclonal antibodies has made it possible to investigate the antigenic structure of the envelope glycoproteins E1 and E2, and to specify their role in the development of antiviral immunity. On the E1 glycoprotein there are five nonoverlapping antigenic sites consisting of eight epitopes that are recognized by monoclonal antibodies; six sites consisting of twenty epitopes were found on the E2 glycoprotein. The monoclonal antibodies ag...
Effects of human alpha interferon on experimentally induced equine herpesvirus-1 infection in horses. The immunotherapeutic effect of low-dose human alpha interferon on viral shedding and clinical disease was evaluated in horses inoculated with equine herpesvirus-1 (EHV-1). Eighteen clinically healthy weanling horses, 5 to 7 months old, were allotted to 3 equal groups. Two groups were treated orally with human alpha-2a interferon (0.22 or 2.2 U/kg of body weight), on days 2 and 1 before inoculation with EHV-1, the day of inoculation, and again on postinoculation day 1. The horses of the remaining group were given a placebo orally on the same days. The horses were monitored daily for changes in...
In vitro antimicrobial activity of defensins against ocular pathogens. New approaches to antimicrobial therapy for ocular pathogens must overcome organisms that are resistant to current therapeutic modalities. This investigation examined the antimicrobial activity of novel antimicrobial neutrophil peptides (defensins NP-1 and NP-5) against isolates from clinical ocular microbial infections in humans and horses. The test panel of human clinical isolates included Candida albicans, an alpha-hemolytic Streptococcus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Morganella morganii. The test panel of equine pathogens included three clinical isolates of P aerug...
Recombinant equine interferon-beta 1: purification and preliminary characterization. Equine interferon-beta 1 (EqIFN-beta 1) was purified from extracts of recombinant Escherichia coli by sequential chromatography on hydroxylapatite, anion-, and cation-exchangers. The resulting protein was greater than 98% pure as determined by sodium dodecylsulfate gel electrophoresis, gel permeation HPLC, and reverse-phase HPLC. Amino-terminal amino acid sequencing revealed that essentially all molecules contained an additional amino-terminal methionine. The specific antiviral activity of EqIFN-beta 1 determined on equine dermal fibroblasts challenged with vesicular stomatitis virus (VSV) was...
Antiviral, anti-glycoprotein and neutralizing antibodies in foals with equine infectious anaemia virus. Equine infectious anaemia virus is related by genome sequence homology to human immunodeficiency virus, caprine arthritis-encephalitis virus and visna virus. Failure of the host to mount a strong neutralizing response detectable in vitro or to eliminate persistent infection in vivo characterizes lentivirus infections in the natural host. In this study the specificities and neutralizing activity of antibodies induced during experimental infection with equine infectious anaemia virus were investigated using antiviral ELISA, radioimmunoprecipitation and neutralization assays. ELISA antibody titre...
Molecular cloning and expression in Escherichia coli of equine type I interferons. Using human interferon-alpha 2 (IFN-alpha 2) and IFN-beta DNA to probe an equine genomic library we isolated recombinant phages containing genes for equine interferon-alpha (EqIFN-alpha), interferon-beta (EqIFN-beta), and interferon-omega (EqIFN-omega). Sequence and hybridization analyses of these genes reveal that the equine genome contains gene families of each of these three type I interferon classes. The mature proteins of EqIFN-alpha are 71-77% homologous to human IFN-alpha polypeptides, and, when expressed in E. coli, possess antiviral activity on both equine and human cells. By contrast...
The spectrum of antiviral activities of acyclovir in vitro and in vivo. In vitro sensitivity data suggest that acyclovir should be effective against clinical manifestations of herpes simplex virus types 1 and 2, varicella-zoster virus and possibly Epstein-Barr virus. The clinical potential against herpes simplex virus types 1 and 2 is further supported by results in animal models. Human cytomegalovirus and the veterinary herpes viruses, with the possible exception of equine herpes virus type 1, may be insufficiently sensitive to be amenable to treatment.
Relative activities of acyclovir and BW759 against Aujeszky’s disease and equine rhinopneumonitis viruses. Compound BW759 (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine) was shown to be about 230 times more active than acyclovir (9-[2-hydroxyethoxymethyl]guanine) (ACV) against Equid herpesvirus type 1 infection in Syrian hamsters and was more effective against Aujeszky's disease in mice. The therapeutic superiority of BW759 over ACV was greater than expected from quantitative inhibitory results in tissue culture with these viruses. When administered to hamsters at dose rates sufficient to prevent any Equid herpesvirus type 1-induced mortality (100 mg of ACV per kg per day; 3 mg of BW759 per kg...
Preliminary characterization of equine interferons and their antiviral activities on bovine, ovine, and human cells. Equine dermal cells induced with poly I:C + DEAE-dextran produced low levels of interferon tentatively classified as equine interferon beta (EqIFN-beta). In contrast, dermal cells initially primed with EqIFN-beta and then superinduced with poly I:C + DEAE-dextran in the presence of cycloheximide and actinomycin D produced greater than 100-fold EqIFN-beta. Equine blood mononuclear cells induced with Newcastle disease virus and phytohemagglutinin produced high levels of interferons tentatively classified as equine interferon alpha (EqIFN-alpha) and equine interferon gamma (EqIFN-gamma), respecti...
Inactivation of equine infectious anemia virus by chemical disinfectants. Twelve chemicals and commercial disinfectants were tested for inactivation of equine infectious anemia virus. In the presence of 10% bovine serum, all chemicals inactivated 4 log10 (based on 0.1 ml) of the virus within 5 minutes at 23 C. A reduction of at least 4 log10 was observed when the virus was exposed for 1 minute to substituted phenolic disinfectants (3 commercial preparations and sodium orthophenylphenate), halogen derivatives (iodophor and sodium hypochlorite), chlorhexidine, and 70% ethanol. Sodium hydroxide (5%), 2% formalin, and 2% glutaraldehyde were slower to inactivate the viru...
[Preparative isolation of alpha 2-macroglobulin, transferrin, albumin and study of their nonspecific gamma-inhibitory activity]. Profiles of distribution of non-specific gamma-inhibitors of influenza A2/Victoria/35/72 in donkey and horse sera were established by gel chromatography in Sephadex G-200. High and low molecular inhibitors were found in 19S and 4S serum fractions. Highly purified preparations of a2-macroglobulin, transferrine and albumin were isolated by a combination of methods of salt precipitation, gel chromatography on Sephadex G-100, G-200 and ion exchange on DEAE-Sephadex A-50. Heating sera resulted in a considerable increase of the antiviral activity of a2-macroglobulin and transferrine and a reduction ...
Effects of crude extracts of various plants on infectious bovine rhinotracheitis virus-plaque production. Extracts of 28 plants were tested without demonstable antiviral activity in an agar-overlay plaque-reduction antiviral assay system, using infectious bovine rhinotracheitis virus and bovine endocardial cell cultures. Ethanolic extract of Narcissus tazetta L bulb elicited antiviral activity by inhibition of viral plaque formation. Antiviral activity was demonstrated against infectious bovine rhinotracheitis and equine rhinopneumonitis viruses. Narcissus tazetta L bulb did not directly inactivate the virus extracellularly. The extract exhibited only limited toxicity to rapidly multiplying bovine...
Elimination of repeated clot formation in mouse ascitic fluid containing arbovirus antibodies. Repeated clot formation in mouse ascitic fluids containing antiviral antibody was eliminated by acid precipitation of the fibrinogen.