RESUMEN
Walleye dermal sarcoma virus (WDSV) is a type of retrovirus, which affects most of the adult walleye fishes during the spawning time. The virus causes multiple epithelial tumors on the fish's skin and fins that are liable for more than 50% of the mortality rate of fish around the world. Till now, no effective antiviral drug or vaccine candidates have been developed that can block the progression of the disease caused by the pathogen. It was found that the 582-amino-acid (aa) residues long internal structural gag polyprotein of the virus plays an important role in virus budding and virion maturation outside of the cell. Inhibition of the protein can block the budding and virion maturation process and can be developed as an antiviral drug candidate against the virus. Therefore, the study aimed to identify potential natural antiviral drug candidates from the tropical mangrove marine plant Avicennia alba, which will be able to block the budding and virion maturation process by inhibiting the activity of the gag protein of the virus. Initially, a homology modeling approach was applied to identify the 3D structure, followed by refinement and validation of the protein. The refined protein structures were then utilized for molecular docking simulation. Eleven phytochemical compounds have been isolated from the marine plant and docked against the virus gag polyprotein. Three compounds, namely Friedlein (CID244297), Phytosterols (CID12303662), and 1-Triacontanol (CID68972) have been selected based on their docking score -8.5 kcal/mol, -8.0 kcal/mol and -7.9 kcal/mol, respectively, and were evaluated through ADME (Absorption, Distribution, Metabolism and Excretion), and toxicity properties. Finally, molecular dynamics (MD) simulation was applied to confirm the binding stability of the protein-ligands complex structure. The ADME and toxicity analysis reveal the efficacy and non-toxic properties of the compounds, where MD simulation confirmed the binding stability of the selected three compounds with the targeted protein. This computational study revealed the virtuous value of the selected three compounds against the targeted gag polyprotein and will be effective and promising antiviral candidates against the pathogen in a significant and worthwhile manner. Although in vitro and in vivo study is required for further evaluation of the compounds against the targeted protein.
Asunto(s)
Antivirales/farmacología , Avicennia/química , Epsilonretrovirus/efectos de los fármacos , Enfermedades de los Peces/prevención & control , Extractos Vegetales/farmacología , Infecciones por Retroviridae/veterinaria , Infecciones Tumorales por Virus/veterinaria , Animales , Antivirales/aislamiento & purificación , Epsilonretrovirus/metabolismo , Epsilonretrovirus/patogenicidad , Enfermedades de los Peces/virología , Productos del Gen gag/antagonistas & inhibidores , Productos del Gen gag/metabolismo , Ligandos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Extractos Vegetales/aislamiento & purificación , Conformación Proteica , Infecciones por Retroviridae/prevención & control , Infecciones por Retroviridae/virología , Relación Estructura-Actividad , Infecciones Tumorales por Virus/prevención & control , Infecciones Tumorales por Virus/virología , Liberación del Virus/efectos de los fármacosRESUMEN
Non-human primates have assumed an important role in preclinical safety assessment studies, particularly in the evaluation of biopharmaceutical and immunomodulatory therapies. Naturally occurring simian retrovirus infections may adversely affect the suitability of primates for use in such studies. Various species of non-human primates are the natural hosts for six exogenous retroviruses, representing five genera within the family Retroviridae. Retroviruses establish persistent infections with a broad spectrum of pathogenic potential, ranging from nonpathogenic to highly pathogenic, depending on the variety of the host, virus, and environmental factors. In the context of immunotoxicology, in which the research objective is to specifically evaluate the effect of drugs or biologics on the immune system, the immune modulatory effects of simian retroviruses, which may be subtle or profound, may introduce significant confounding into the studies of immunotoxic effects utilizing non-human primates. Latent or subclinical retrovirus infections are common and research-related procedures may lead to virus reactivation or overt disease. Adverse effects of undetected retrovirus infections on preclinical research include the loss of experimental subjects (and potentially of statistical power) due to increased morbidity and mortality, virus-induced clinical abnormalities, histologic lesions, alteration of physiologic parameters and biologic responses, and interference with in vitro assays and/or cytolytic destruction of primary cell cultures. The aim of this review is to provide an overview of the key biological, clinical, and pathological features of several important simian retroviruses, with emphasis on viruses infecting macaques and other primate species commonly used in preclinical research, and a discussion of the implications of these infections for immunotoxicology and other preclinical research in primates. Adequate pre-study retrovirus screening is essential to exclude retrovirus-infected primates from research protocols.
Asunto(s)
Haplorrinos/virología , Sistema Inmunológico/efectos de los fármacos , Enfermedades de los Monos/virología , Infecciones por Retroviridae/veterinaria , Retrovirus de los Simios/patogenicidad , Infecciones Tumorales por Virus/veterinaria , Xenobióticos/toxicidad , Animales , Animales de Laboratorio , Evaluación Preclínica de Medicamentos , Sistema Inmunológico/fisiología , Sistema Inmunológico/virología , Enfermedades de los Monos/patología , Infecciones por Retroviridae/patología , Infecciones por Retroviridae/transmisión , Retrovirus de los Simios/aislamiento & purificación , Retrovirus de los Simios/fisiología , Pruebas de Toxicidad , Infecciones Tumorales por Virus/patología , Infecciones Tumorales por Virus/transmisión , Xenobióticos/clasificaciónRESUMEN
The effects of fig tree latex in treating teat papillomatosis in cow in comparison with salicylic acid were evaluated. For this purpose, 12 cows of 1-3 years of age (average 2.25) affected by teat papillomatosis were divided into three groups. In group A, four cows were treated by fig tree (Ficus carica) latex; in group B, four cows were treated with 10% salicylic acid solution and in group C, four cows were kept as control animals receiving no treatment. Animals in each treatment group received their treatment once every 5 days. In groups A and B, de-epithelialization and shrinking of the warts began from the fifth day of treatment and all the warts disappeared within 30 days. However, in the control group no changes in the number of warts were observed until day 15 but thereafter a number of warts disappeared spontaneously in some of the animals. Both salicylic acid and fig tree latex were evaluated as having similar therapeutic effects in treating teat papillomatosis in cow.
Asunto(s)
Enfermedades de los Bovinos/tratamiento farmacológico , Ficus , Látex/administración & dosificación , Infecciones por Papillomavirus/veterinaria , Fitoterapia , Infecciones Tumorales por Virus/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/patología , Femenino , Glándulas Mamarias Animales , Papillomaviridae , Infecciones por Papillomavirus/tratamiento farmacológico , Ácido Salicílico/administración & dosificación , Resultado del Tratamiento , Infecciones Tumorales por Virus/tratamiento farmacológicoRESUMEN
Secretions and excretions from cattle with persistent bovine leukemia virus (BLV) infections were tested for BLV by inoculation into sheep. Development of antibody to the BLV glycoprotein antigen and reisolation of virus from peripheral blood leukocytes were the two criteria used to confirm infection in test sheep. The virus was detected in milk from 4 of 6 cows examined and in colostrum from 1 of 4 cows examined. The virus was not detected in semen from 8 bulls or in nasal secretions, saliva, and urine from 2 cows.