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.
Efficacy of a single intravenous dose of the neuraminidase inhibitor peramivir in the treatment of equine influenza. Equine influenza A virus (EIV) of the H3N8 subtype is an important pathogen causing acute respiratory disease in horses. Peramivir is a selective inhibitor of the influenza virus neuraminidase (NA). The characteristics of peramivir are not only its capacity for parenteral administration, but also its strong affinity for NA and slow off-rate from the NA-peramivir complex, suggesting that it could lead to a prolonged inhibitory effect and thus allow a lower dosing frequency. The aims of this study were to evaluate the inhibitory efficacy of peramivir against the NA activities of EIV in vitro and...
Evaluation of the antiviral activity of (1’S,2’R)-9-[[1′,2′-bis(hydroxymethyl)cycloprop-1′-yl]methyl]guanine (A-5021) against equine herpesvirus type 1 in cell monolayers and equine nasal mucosal explants. Equine herpesvirus 1 (EHV1) is a ubiquitous equine alphaherpesvirus that causes respiratory disease, neurological symptoms and abortions. Current vaccines are not fully protective and effective therapeutics are lacking. A-5021 [(1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guanine], previously shown to possess potent anti-herpetic activity against most human herpesviruses, was evaluated for its potential to inhibit EHV1 replication. In equine embryonic lung (EEL) cells, infected with either a non-neurovirulent (97P70) or a neurovirulent (03P37) EHV1 isolate, A-5021 proved to be ...
Quantification of Equid herpesvirus 5 DNA in clinical and necropsy specimens collected from a horse with equine multinodular pulmonary fibrosis. A 15-year-old Belgian gelding was referred for fever, depression, and respiratory distress. Lung biopsy revealed interstitial fibrosis consistent with chronic interstitial pneumonia. Equid herpesvirus 5 (EHV-5) DNA was detected by polymerase chain reaction (PCR) in bronchoalveolar lavage and biopsy specimens. A presumptive diagnosis of equine multinodular pulmonary fibrosis (EMPF) was made, and the horse was administered a systemic treatment with corticosteroids and antiviral drugs. Despite initial clinical improvement, 4 weeks later, the condition of the horse rapidly deteriorated, and the an...
Successful treatment of equine sarcoids by topical aciclovir application. Based on the anecdotally reported eradication of a sarcoid using aciclovir cream, the curative potential of this ointment was investigated in 22 sarcoid-affected horses referred to the Equine Clinic Tillysburg, Austria, between 2006 and 2009. Sarcoid disease was diagnosed by clinical examination and bovine papillomavirus types 1 and 2 from intact skin and tumour tissue. As nine horses had more than one lesion, a total of 47 sarcoids were treated by daily topical application of aciclovir 5 per cent cream for a period of two to six months; in four horses, surgical tumour ablation was performed b...
Report of the Second Havemeyer EHV-1 Workshop, Steamboat Springs, Colorado, USA, September 2008. This report summarises the findings of the Second Havemeyer EHV-1 Workshop, which was held in Steamboat Springs, Colorado, USA in September 2008. A total of 38 delegates, consisting of veterinary clinicians and scientists from academia and industry participated in a series of sessions that focused on equine herpesvirus myeloencephalopathy (EHM). Each session consisted of a review, followed by short presentations on current research topics. The sessions included EHM epidemiology, in vivo and in vitro models for studying EHM, EHV-1 virulence determinants, real-time PCR diagnostics, antiviral med...
The efficacy of imiquimod 5% cream (Aldara® in the treatment of aural plaque in horses: a pilot open-label clinical trial. Aural plaques affect at least 22% of horses and can be asymptomatic or cause ear sensitivity. Immunohistochemical and electron microscopy studies have shown a strong association between aural plaques and papilloma virus. The purpose of this study was to investigate the efficacy of imiquimod 5% cream, an immune response modifier with potent antiviral activity, in the treatment of equine aural plaques. Twenty-one horses were enrolled and 16 completed the study. Imiquimod 5% cream was applied three times a week, every other week. When both ears were affected only the worst affected ear was treate...
Curing of HeLa cells persistently infected with equine arteritis virus by a peptide-conjugated morpholino oligomer. A significant consequence of equine arteritis virus (EAV) infection of horses is persistence of the virus in a variable percentage of infected stallions. We recently established an in vitro model of EAV persistence in cell culture for the purpose of furthering our understanding of EAV biology in general and viral persistence in the stallion in particular. In this study we investigated whether persistently infected HeLa cells could be cured of EAV infection by treatment with an antisense peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) designed to target the 5'-terminal region o...
Residue 752 in DNA polymerase of equine herpesvirus type 1 is non-essential for virus growth in vitro. A single amino acid variation in the equine herpesvirus type 1 (EHV-1) DNA polymerase (Pol) (D752/N752) determines its neuropathogenic potential. Here, an EHV-1 strain RacL11 mutant with a deletion of Pol residue 752 was constructed. The deletion virus was then repaired to encode D752 or N752, respectively. The Delta752 mutant virus replicated with kinetics indistinguishable from those of D752 and N752 viruses. In addition, we could demonstrate that the deletion mutant was significantly more resistant to aphidicolin, a drug targeting Pol, compared with the N752 but not the D752 variant. In equ...
Alphavirus antiviral drug development: scientific gap analysis and prospective research areas. The New World alphaviruses Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV) pose a significant threat to human health as the etiological agents of serious viral encephalitis through natural infection as well as through their potential use as a biological weapon. At present, there is no FDA-approved medical treatment for infection with these viruses. The Defense Threat Reduction Agency, Joint Science and Technology Office for Chemical and Biological Defense (DTRA/JSTO), is currently funding research aimed at deve...
Pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses. We investigated the pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses. Following an oral dose of famciclovir at 20 mg/kg, maximum plasma concentrations of penciclovir occurred between 0.75 and 1.5 hr (mean 0.94 + or - 0.38 hr) after dosing and were in the range 2.22 to 3.56 microg/ml (mean 2.87 + or - 0.61 microg/ml). The concentrations of penciclovir declined in a biphasic manner after the peak concentration was attained. The mean half-life of the rapid elimination phase was 1.73 + or - 0.34 hr whereas that of the slow elimination phase was 34.34 +...
Characterization of a thymidine kinase-deficient mutant of equine herpesvirus 4 and in vitro susceptibility of the virus to antiviral agents. Equine herpesvirus 4 (EHV-4) is an important equine pathogen that causes respiratory tract disease among horses worldwide. A thymidine kinase (TK)-deletion mutant has been generated by using bacterial artificial chromosome (BAC) technology to investigate the role of TK in pathogenesis. Deletion of TK had virtually no effect on the growth characteristics of WA79DeltaTK in cell culture when compared to the parent virus. Also, virus titers and plaque formation were unaffected in the absence of the TK gene. The sensitivity of EHV-4 to inhibition by acyclovir (ACV) and ganciclovir (GCV) was studied...
Antiviral effect of recombinant equine interferon-gamma on several equine viruses. Recombinant equine interferon-gamma (reIFN-gamma) was prepared using a baculovirus expression system and its antiviral activity was investigated using several equine viruses. The reIFN-gamma suppressed the replication of all equine viruses used in the present experiment in horse cell cultures, but did not affect the growth of host cells at concentrations of less than 1000 u/ml. A strong antiviral effect was observed, especially against RNA viruses. Equine picornavirus, equine rhinovirus and equine arteritis virus could not be propagated at all in 100 u/ml reIFN-gamma when 100 TCID(50) of infec...
The effect of siRNA treatment on experimental equine herpesvirus type 1 (EHV-1) infection in horses. Available vaccines fail to induce lasting and protective immunity to equine herpesvirus 1 (EHV-1) associated diseases. RNA interference is a novel approach showing promise for therapeutic use in outbreak situations. This study examined the effect of small interfering RNA (siRNA) on clinical signs as well as the presence of live virus and viral DNA in nasal secretions and peripheral blood mononuclear cells (PBMCs) in horses experimentally infected with EHV-1. siRNA targeting two EHV-1 genes (glycoprotein B and the origin binding protein) was administered 12h before and 12h after intranasal infe...
Multiple oral dosing of valacyclovir in horses and ponies. The aim of the current study was to investigate whether multiple oral dosing of valacyclovir could result in plasma concentrations exceeding the EC(50)-value of acyclovir against equine herpesvirus 1 (EHV1) during the majority of the treatment period. Additionally, we wanted to determine the concentration of acyclovir in nasal mucus and cerebrospinal fluid (CSF). Valacyclovir was administered to four horses and two ponies, three times daily, at a dosage of 40 mg/kg, for four consecutive days. Blood was collected prior to each administration and 1 h after dosing. Nasal mucus samples and CSF wer...
Small interfering RNA targeting bovine papillomavirus type 1 E2 induces apoptosis in equine sarcoid transformed fibroblasts. Equine sarcoids are skin tumours of horses caused by infection with BPV-1 or 2. Maintenance and replication of the viral genome depend upon the viral proteins E1 and E2. We examined the effects of an E2 specific siRNA on E2 and E1 viral gene expression, viral load and cell growth in BPV-1 transformed sarcoid-derived cells. Transfection with E2-siRNA caused a reduction in E2 and E1 mRNA expression as well as viral load, growth inhibition and decreased anchorage-independent growth. siRNA treated cells showed significantly higher apoptosis rates than control cells. Thus sequence specific targetin...
Expression of biologically active recombinant equine interferon-gamma in Escherichia coli. Interferon gamma (IFN-gamma) is a pleiotropic cytokine that is recognized as an important modulator of the immune response. To date, there is no report that prokaryocyte-derived recombinant equine IFN-gamma has antiviral activity. In this report, the gene coding equine IFN-gamma (EIFN-gamma) mature protein was cloned into pET-28a (+) and the recombinant EIFN-gamma was expressed in Escherichia coli (E. coli). The antiviral activity of expressed recombinant EIFN-gamma was evaluated by using a recombinant Vesicular Stomatitis Virus expressing green fluorescence protein (rVSV-GFP) system in the eq...
Structural model of the Rev regulatory protein from equine infectious anemia virus. Rev is an essential regulatory protein in the equine infectious anemia virus (EIAV) and other lentiviruses, including HIV-1. It binds incompletely spliced viral mRNAs and shuttles them from the nucleus to the cytoplasm, a critical prerequisite for the production of viral structural proteins and genomic RNA. Despite its important role in production of infectious virus, the development of antiviral therapies directed against Rev has been hampered by the lack of an experimentally-determined structure of the full length protein. We have used a combined computational and biochemical approach to gen...
Effective treatment of respiratory alphaherpesvirus infection using RNA interference. Equine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA's), delivered intranasally, could prove a valuable alternative for infection control. siRNA's against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrea...
RNA interference protects horse cells in vitro from infection with Equine Arteritis Virus. Equine Arteritis Virus (EAV) belongs to the Arteriviridae and causes viral arteritis in horses. In an attempt to develop novel and save therapies against the infection it was tested whether EAV is susceptible to RNA interference (RNAi) in an equine in vitro system. Horse cells were transfected with chemically synthesized small interfering RNA oligonucleotides (siRNAs) and challenged with EAV. Application of these siRNAs led to a significant protection of the cells, and virus titers decreased drastically. siRNAs derived from DNA plasmids expressing small hairpin RNAs (shRNAs) were also effectiv...
Equine infectious anemia virus resists the antiretroviral activity of equine APOBEC3 proteins through a packaging-independent mechanism. Equine infectious anemia virus (EIAV), uniquely among lentiviruses, does not encode a vif gene product. Other lentiviruses, including human immunodeficiency virus type 1 (HIV-1), use Vif to neutralize members of the APOBEC3 (A3) family of intrinsic immunity factors that would otherwise inhibit viral infectivity. This suggests either that equine cells infected by EIAV in vivo do not express active A3 proteins or that EIAV has developed a novel mechanism to avoid inhibition by equine A3 (eA3). Here, we demonstrate that horses encode six distinct A3 proteins, four of which contain a single copy o...
Evaluation of orally administered valacyclovir in experimentally EHV1-infected ponies. The purpose of the current study was to investigate the therapeutic efficacy of valacyclovir against EHV1 in a controlled study. Eight naïve Shetland ponies were inoculated with 10(6.5) TCID(50) of the neuropathogenic strain 03P37. Four ponies were treated with valacyclovir at a dosage of 40mg/kg bodyweight, 3 times daily, for 5 (n=2) or 7 (n=2) consecutive days, while the other four ponies served as untreated controls. The treatment regimen started 1h before inoculation. Ponies were monitored daily for clinical signs. At 0, 1, 2, 3, 4, 5, 7, 9, 11, 14, 17 and 21 days post inoculation (d pi),...
Pharmacokinetics of valacyclovir in the adult horse. Recent outbreaks of equine herpes virus type-1 infections have stimulated renewed interest in the use of effective antiherpetic drugs in horses. The purpose of this study was to investigate the pharmacokinetics of valacyclovir (VCV), the prodrug of acyclovir (ACV), in horses. Six adult horses were used in a randomized cross-over design. Treatments consisted of 10 mg/kg ACV infused intravenously, 5 g (7.7-11.7 mg/kg) VCV delivered intragastrically (IG) and 15 g (22.7-34.1 mg/kg) VCV administered IG. Serum samples were obtained at predetermined times for acyclovir assay using high-performance li...
Venezuelan equine encephalitis virus capsid protein inhibits nuclear import in Mammalian but not in mosquito cells. Venezuelan equine encephalitis virus (VEEV) represents a continuous public health threat in the United States. It has the ability to cause fatal disease in humans and in horses and other domestic animals. We recently demonstrated that replicating VEEV interferes with cellular transcription and uses this phenomenon as a means of downregulating a cellular antiviral response. VEEV capsid protein was found to play a critical role in this process, and its approximately 35-amino-acid-long peptide, fused with green fluorescent protein, functioned as efficiently as did the entire capsid. We detected a...
Evaluation of the safety, immunogenicity and pharmacokinetics of equine anti-SARS-CoV F(ab’)(2) in macaque. To warrant potential clinical testing, the equine anti-SARS-CoV F(ab')(2) requires evaluation in as many animal models as possible and a safety test in a primate model. In this study, we evaluated the pharmacokinetics, tolerance and immunity of this kind of antibody in macaques and rats. Results showed that the F(ab')(2) fragments had a normal metabolism in injected animals. The general physiological indexes did not differ between animals injected with anti-SARS-CoV F(ab')(2) or saline. However, a mild inflammatory response in local injection site and a moderate immune response against this an...
Analysis of Venezuelan equine encephalitis virus capsid protein function in the inhibition of cellular transcription. The encephalitogenic New World alphaviruses, including Venezuelan (VEEV), eastern (EEEV), and western equine encephalitis viruses, constitute a continuing public health threat in the United States. They circulate in Central, South, and North America and have the ability to cause fatal disease in humans and in horses and other domestic animals. We recently demonstrated that these viruses have developed the ability to interfere with cellular transcription and use it as a means of downregulating a cellular antiviral response. The results of the present study suggest that the N-terminal, approxima...
Pharmacokinetics of acyclovir after intravenous infusion of acyclovir and after oral administration of acyclovir and its prodrug valacyclovir in healthy adult horses. The purpose of this study was twofold. The first aim was to evaluate the oral bioavailability and pharmacokinetics (PKs) of acyclovir in horses after intravenous (i.v.) administration and after oral administration of acyclovir and its prodrug, valacyclovir. Second, we aimed to combine these PK data with pharmacodynamic (PD) information, i.e., 50% effective concentrations (EC(50) values) from in vitro studies, to design an optimal dosage schedule. Three treatments were administered to healthy adult horses: 10 mg of acyclovir/kg of body weight delivered as an i.v. infusion over 1 h, 20 mg of acy...
A novel horse alpha-defensin: gene transcription, recombinant expression and characterization of the structure and function. Defensins are a predominant class of antimicrobial peptides, which act as endogenous antibiotics. Defensins are classified into three distinct sub-families: theta-, beta-, and alpha-defensins. Synthesis of alpha-defensin has been confirmed only in primates and glires to date and is presumably unique for a few tissues, including neutrophils and Paneth cells of the small intestine. Antimicrobial activities of these peptides were shown against a wide variety of microbes including bacteria, fungi, viruses and protozoan parasites. In the present study, we report the characterization of the equine a...
Clinical pharmacokinetics of oseltamivir and its active metabolite oseltamivir carboxylate after oral administration in horses. The aim of this study was to investigate the pharmacokinetics of oseltamivir carboxylate (OC) in horses (n=6) after oral administration of its prodrug oseltamivir. The binding rate of OC to horse plasma proteins was negligible (<1%). Oral administration of oseltamivir of 2 mg/kg body weight of oseltamivir to horses provided a plasma concentration of OC (mean maximum concentration: 257.9 ng/ml) above the inhibitory concentrations against equine influenza A viruses determined in vitro. However, because OC is rapidly eliminated from horse plasma (mean elimination half-life: 2.5 hr), administratio...
Outbreak of neurologic disease caused by equine herpesvirus-1 at a university equestrian center. Equine herpesvirus type 1 (EHV-1) infection causes neurologic disease in horses. However, risk factors for the disease and long-term prognosis are poorly characterized. Objective: There are identifiable risk factors for equine herpes-1 myeloencephalopathy. Methods: The entire population of 135 horses housed within the equestrian facility. Methods: A descriptive study investigated the clinical, serologic, virologic, and management aspects of an outbreak of EHV-1 myeloencephalopathy. Results: Out of 135 horses at the facility, 117 displayed signs of EHV-1 infection. Forty-six horses developed ne...