RESUMO
Phytotherapy has been used to treat a different type of diseases including cancer for a long time, and it was a source for different active anti-tumor agents. Oncolytic Newcastle disease virus (AMHA1) are very promising anti-tumor therapy. Nevertheless, NDV-based monotherapeutics have not been very useful to some resistant tumors. Thus, the efficiency of oncolytic NDV must enhance by combining NDV with other novel therapies. The current study aimed to determine the possibility of improving the oncolytic effect induced by NDV through Rheum ribes rhizomes extract administration in vitro and in vivo. Methods, the in vitro study include exposure of the crude extract of Rheum ribes alone or NDV alone or combination of both agents for 72 h. The cancer cells tested were murine mammary adenocarcinoma AMN3, Human Rhabdomyosarcoma RD, and Human Glioblastoma AMGM5, and using rat embryo fibroblast REF as normal control cells. MTT cell viability assay was used and analyzed for possible synergism using the Chou-Talalay analysis method. In vivo experiment included study the combination and the monotherapeutic modalities in the transplanted murine mammary adenocarcinoma AM3 line and tumor sections analyzed by histopathology. Results, Combination therapy of NDV-R. ribes showed enhanced oncolytic activity on cancer cells. With no cytotoxicity on normal cells. In vivo study showed that monotherapeutic modalities had lower growth inhibitory effect on transplanted tumors in mice in compare to combination therapy. Histopathological examination revealed the broader area of necrosis in tumors treated by combination therapy. In conclusion, the novel combination recommended for clinical application for cancer therapy.
Assuntos
Adenocarcinoma/terapia , Neoplasias Mamárias Experimentais/terapia , Terapia Viral Oncolítica/métodos , Extratos Vegetais/farmacologia , Rheum/química , Rizoma/química , Adenocarcinoma/patologia , Animais , Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada/métodos , Feminino , Humanos , Neoplasias Mamárias Experimentais/patologia , Camundongos , Vírus da Doença de Newcastle/fisiologia , Vírus Oncolíticos/fisiologia , Ratos , Resultado do TratamentoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Synthetic antiviral drugs have several limitations including high cost. Thus research on antiviral property of medicinal plants is continuously gaining importance. Polyalthia longifolia possesses several medicinal properties and has been used in traditional ayurvedic medicine for treatment of dermatological ailments as kushta, visarpa/herpes virus infection and also to treat pyrexia of unknown origin as mentioned in Visarpa Chikitsa. AIM OF THE STUDY: Keeping in view the cytotoxic, anti-cancer activity and antiviral efficacy of Polyalthia longifolia against herpes, present study was undertaken to evaluate the in vitro antiviral activity of methanolic extract of Polyalthia longifolia leaves, if any, and to unravel the possible target(s)/mechanism of action. MATERIAL AND METHODS: Antiviral activity of Polyalthia longifolia methanolic extract was studied using Vero cell lines against paramyxoviruses, namely-peste des petits ruminants virus (PPRV) and Newcastle disease virus (NDV). Cytotoxicity of the test extract was evaluated employing MTT assay. Virucidal activity, and viral-attachment, virus entry and release assays were determined in Vero cells using standard experimental protocols. The viral RNA in the virus-infected cells was quantified by qRT-PCR. RESULTS: At non-cytotoxic concentration, methanolic extract of Polyalthia longifolia leaves was found to inhibit the replication of PPRV and NDV at viral entry and budding level, whereas other steps of viral life cycle such as attachment and RNA synthesis remained unaffected. CONCLUSIONS: Polyalthia longifolia leaves extract possesses promising antiviral activity against paramyxoviruses and acts by inhibiting the entry and budding of viruses; and this plant extract evidently possesses excellent and promising potential for development of effective herbal antiviral drug.
Assuntos
Antivirais/farmacologia , Vírus da Doença de Newcastle/efeitos dos fármacos , Vírus da Peste dos Pequenos Ruminantes/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polyalthia , Animais , Chlorocebus aethiops , Vírus da Doença de Newcastle/fisiologia , Vírus da Peste dos Pequenos Ruminantes/fisiologia , Folhas de Planta , Células Vero , Internalização do Vírus/efeitos dos fármacosRESUMO
BACKGROUND: Medicinal mushrooms contain biologically active substances that can be used as an immune-modulating agent in poultry. The present study aimed to investigate the effects of Flammulina velutipes mushroom waste (FVW) on performance, immune response and serum immunity in growing layer hens. RESULTS: No significant differences (P > 0.05) were observed with respect to average daily feed intake, body weight gain and feed conversion ratio among the experimental groups during the entire study period (1-70 days). Antibody titers against Newcastle disease and infectious bronchitis were higher (P < 0.05) in the FVW fed groups than in the control and antibiotic groups. On day 28, serum immunoglobulin (Ig)A and IgG were higher (P < 0.05) in the 6% FVW group than in the control and antibiotic fed groups. On day 70, serum IgA was higher (P < 0.05) in FVW fed groups than in the control group; IgG was higher (P < 0.05) in the FVW groups than in the control and antibiotic groups. However, IgM was higher (P < 0.05) in both the 4% and 6% FVW groups than in the control and antibiotic groups for both experimental periods. Serum cytokine interleukin (IL)-2 and tumor necrosis factor-α concentrations were significantly higher (P < 0.05) in both the 4% and 6% FVW grousp than in the control and antibiotic groups; IL-4 was significantly higher (P < 0.05) in the FVW groups than in the control group; and IL-6 was significantly higher (P < 0.05) in the 6% FVW group than in the control and antibiotic groups. CONCLUSION: FVW at the 6% level can be used as a potential phytogenic feed stuff in growing layer hen rations with respect to improving the immune response without affecting normal weight gain. © 2018 Society of Chemical Industry.
Assuntos
Ração Animal/análise , Galinhas/crescimento & desenvolvimento , Suplementos Nutricionais/análise , Flammulina/química , Imunidade Humoral , Doenças das Aves Domésticas/imunologia , Resíduos/análise , Animais , Anticorpos Antivirais/imunologia , Galinhas/imunologia , Galinhas/metabolismo , Galinhas/virologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Feminino , Flammulina/metabolismo , Vírus da Bronquite Infecciosa/imunologia , Vírus da Bronquite Infecciosa/fisiologia , Doença de Newcastle/imunologia , Doença de Newcastle/fisiopatologia , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/fisiologia , Doenças das Aves Domésticas/fisiopatologia , Doenças das Aves Domésticas/virologiaRESUMO
Newcastle disease (ND), characterized by visceral, respiratory, and neurological pathologies, causes heavy economic loss in the poultry industry around the globe. While significant advances have been made in effective diagnosis and vaccine development, molecular mechanisms of ND virus (NDV)-induced neuropathologies remain elusive. In this study, we report the magnitude of oxidative stress and histopathological changes induced by the virulent NDV (ZJ1 strain) and assess the impact of vitamin E in alleviating these pathologies. Comparative profiling of plasma and brains from mock and NDV-infected chicken demonstrated alterations in several oxidative stress makers such as nitric oxide, glutathione, malondialdehyde, total antioxidant capacity, glutathione S-transferase, superoxide dismutase, and catalases. While decreased levels of glutathione and total antioxidant capacity and increased concentrations of malondialdehyde and nitric oxide were observed in NDV-challenged birds at all time points, these alterations were eminent at latter time points (5 days post infection). Additionally, significant decreases in the activities of glutathione S-transferase, superoxide dismutase, and catalase were observed in the plasma and brains collected from NDV-infected chickens. Intriguingly, we observed that supplementation of vitamin E can significantly reduce the alteration of oxidative stress parameters. Under NDV infection, extensive histopathological alterations were observed in chicken brain including neural inflammation, capillary hyperemia, necrosis, and loss of prominent axons, which were reduced with the treatment of vitamin E. Taken together, our findings highlight that neurotropic NDV induces extensive tissue damage in the brain and alters plasma oxidative stress profiles. These findings also demonstrate that supplementing vitamin E ameliorates these pathologies in chickens and proposes its supplementation for NDV-induced stresses.
Assuntos
Galinhas/virologia , Suplementos Nutricionais , Doença de Newcastle/metabolismo , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/efeitos dos fármacos , Vírus da Doença de Newcastle/fisiologia , Estresse Oxidativo , Vitamina E/administração & dosagem , Animais , Antioxidantes/metabolismo , Biomarcadores , Biópsia , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/virologia , Doença de Newcastle/patologia , Óxido Nítrico/metabolismo , Especificidade de Órgãos , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Carga ViralRESUMO
The progressive decrease in the efficiency of synthetic drugs has prompted research into phytogenic feed additives with potentially immunomodulatory and anti-infective properties. Complex diseases with a mixed etiology, including viral, pose a growing problem in domestic pigeons. The aim of this study was to determine the effectiveness of various doses of aloe vera and licorice extracts on the course of experimental PPMV-1 infection in pigeons. The experiment was performed on pigeons divided into 5 groups, including one control group and 4 experimental groups, which were orally administered aloe vera or licorice extracts at 300 or 500 mg/kg BW for 7 d after experimental inoculation with PPMV-1. On d 4, 7, and 14 after inoculation, cloacal swabs and samples of organs were collected from 4 birds in each group. The samples were analyzed to determine the copy number of PPMV-1 RNA by TaqMan qPCR. The results indicate that licorice and aloe vera extracts inhibited PPMV-1 replication by decreasing viral RNA copy numbers in the examined organs. The most inhibitory effect was observed in pigeons receiving aloe vera extract at 300 mg/kg BW, for which PPMV-1 RNA copy numbers were approximately 7-fold lower (brain), 9-fold lower (kidneys), and 14-fold lower (liver) than in the control group. The results of this study point to the potentially antiviral effects of aloe vera and licorice extracts in pigeons infected with PPMV-1. To the best of our knowledge, this is the first study to investigate the antiviral properties of aloe vera and licorice extracts in domestic pigeons.
Assuntos
Aloe/química , Columbidae , Glycyrrhiza/química , Doença de Newcastle/tratamento farmacológico , Vírus da Doença de Newcastle/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Relação Dose-Resposta a Droga , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/fisiologiaRESUMO
The present study was aimed at investigating the therapeutic efficacy of vitamin E on oxidative injury in brain and liver of Newcastle disease virus (NDV) challenged chickens. We have analyzed the xanthine oxidase (XOD) activity; uric acid (UA) levels and superoxide radical generation by using electron spin resonance spectroscopy. Further, protein oxidation, nitration and apoptosis were evaluated in the brain and liver of the control, NDV-infected and NDV+Vit. E treated groups. A significant elevation was observed in XOD activity and UA levels in brain (p<0.001) and liver (p<0.05) of NDV infected birds when compared to controls. Further, significant increase in the production of superoxides, enhanced intracellular protein carbonyls and nitrates were observed in the brain and liver of NDV-infected birds over healthy subjects. Apoptosis studies also suggested that a larger number of TUNEL positive cells were observed in brain and a moderately in liver of NDV-infected chickens. However, all these perturbations were significantly ameliorated in NDV+Vit. E treated chickens as compared to NDV-infected birds. Taken together, our results suggested that NDV-induced neuronal and hepatic damage at least in part mediates oxidative stress and on the other hand, supplementation of vitamin E mitigates NDV-induced oxidative damage thereby protects brain and liver of chickens. These findings could provide new insights into the understanding of NDV pathogenesis and therapeutic effects of dietary antioxidants.
Assuntos
Encéfalo/metabolismo , Sequestradores de Radicais Livres/farmacologia , Fígado/metabolismo , Doença de Newcastle/metabolismo , Doenças das Aves Domésticas/metabolismo , Vitamina E/farmacologia , Animais , Apoptose , Proteínas Aviárias/metabolismo , Encéfalo/patologia , Encéfalo/virologia , Células Cultivadas , Galinhas , Avaliação Pré-Clínica de Medicamentos , Sequestradores de Radicais Livres/uso terapêutico , Fígado/patologia , Fígado/virologia , Masculino , Doença de Newcastle/tratamento farmacológico , Vírus da Doença de Newcastle/fisiologia , Especificidade de Órgãos , Oxirredução , Estresse Oxidativo , Carbonilação Proteica , Vitamina E/uso terapêutico , Xantina Oxidase/metabolismoRESUMO
Epimedium koreanum Nakai has been extensively used in traditional Korean and Chinese medicine to treat a variety of diseases. Despite the plant's known immune modulatory potential and chemical make-up, scientific information on its antiviral properties and mode of action have not been completely investigated. In this study, the broad antiviral spectrum and mode of action of an aqueous extract from Epimedium koreanum Nakai was evaluated in vitro, and moreover, the protective effect against divergent influenza A subtypes was determined in BALB/c mice. An effective dose of Epimedium koreanum Nakai markedly reduced the replication of Influenza A Virus (PR8), Vesicular Stomatitis Virus (VSV), Herpes Simplex Virus (HSV) and Newcastle Disease Virus (NDV) in RAW264.7 and HEK293T cells. Mechanically, we found that an aqueous extract from Epimedium koreanum Nakai induced the secretion of type I IFN and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in cells. Among various components present in the extract, quercetin was confirmed to have striking antiviral properties. The oral administration of Epimedium koreanum Nakai exhibited preventive effects on BALB/c mice against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2). Therefore, an extract of Epimedium koreanum Nakai and its components play roles as immunomodulators in the innate immune response, and may be potential candidates for prophylactic or therapeutic treatments against diverse viruses in animal and humans.
Assuntos
Antivirais/farmacologia , Antivirais/uso terapêutico , Epimedium/química , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Animais , Antivirais/isolamento & purificação , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/virologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Fatores Imunológicos/isolamento & purificação , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/fisiologia , Macrófagos/imunologia , Macrófagos/virologia , Camundongos Endogâmicos BALB C , Vírus da Doença de Newcastle/efeitos dos fármacos , Vírus da Doença de Newcastle/fisiologia , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/virologia , Extratos Vegetais/isolamento & purificação , Simplexvirus/efeitos dos fármacos , Simplexvirus/fisiologia , Análise de Sobrevida , Vesiculovirus/efeitos dos fármacos , Vesiculovirus/fisiologia , Replicação Viral/efeitos dos fármacosRESUMO
Newcastle disease virus (NDV) belonging to the Paramyxovirinae subfamily is one of the most devastating pathogens in poultry. Although vaccines are widely applied to control the infection, outbreaks of Newcastle disease (ND) repeatedly happen. Currently, there are no alternative control measures available for ND. In the present study, we found that sulfated Chuanmingshen violaceum polysaccharide (sCVPS) were potent inhibitors of NDV in specific pathogen free chickens infected with a virulent strain. With sCVPS treatment, the survival rate increased by almost 20% and virus titers in test organs, including brain, lung, spleen and thymus, were significantly decreased. The sCVPS also exhibited the ability to prevent viral transmission by reducing the amount of virus shed in saliva and feces. Higher concentrations of interferon α and γ in serum were detected in chickens treated with sCVPS, indicating that one of the antiviral mechanisms may be attributed to the property of immunoenhancement. Histopathological examination showed that sCVPS could alleviate the tissue lesions caused by NDV infection. These results suggest that sCVPS are expected to be a new alternative control measure for NDV infection and further studies could be carried out to evaluate the antiviral activity of sCVPS against other paramyxoviruses.
Assuntos
Antivirais/farmacologia , Apiaceae/química , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Doenças das Aves Domésticas/virologia , Animais , Antivirais/química , Galinhas , Interferons/sangue , Doença de Newcastle/sangue , Doença de Newcastle/tratamento farmacológico , Doença de Newcastle/mortalidade , Vírus da Doença de Newcastle/fisiologia , Extratos Vegetais/química , Polissacarídeos/química , Doenças das Aves Domésticas/sangue , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/mortalidade , Eliminação de Partículas Virais/efeitos dos fármacosRESUMO
Co-infection of reticuloendotheliosis virus (REV) and avian leukosis virus subgroup J (ALV-J), which can cause suppressed immunity and vaccination failure, frequently occurs in chicken flocks in China. Taishan Pinus massoniana pollen polysaccharide (TPPPS) and propolis (PP) have been proven to possess immune modulatory effects and improve the immune effects of vaccines. This study aimed to investigate the immune modulatory ability of TPPPS and PP on chickens co-infected with immunosuppressive viruses. Prior to the study, chickens were artificially established as REV and ALV-J co-infection models. Four randomly assigned groups of these immunosuppressed chickens were successively administered with TPPPS, PP, mixture of TPPPS and PP (TPPPS-PP), or phosphate-buffered saline (PBS) for three days. At nine days old, the four immunosuppressed groups, as well as one normal group, were inoculated with the attenuated Newcastle disease (ND) vaccine. During the monitoring period, the indices of immune organ weight, lymphocyte transformation rates, CD4(+) and CD8(+) T-lymphocyte counts in peripheral blood, IL-2 and IFN-γ secretions, serum antibody titers of ND vaccine, and viral loads in spleens were determined. The results showed that chickens administered with TPPPS, PP, or TPPPS-PP could significantly enhance the levels of the above immune parameters compared to chickens in the PBS group. We observed the strongest immunity in the TPPPS-PP group, which indicates that the combination of TPPPS and PP versus TPPPS or PP alone, could generate better effects on improving the immune system effectiveness of immunosuppressed chickens.
Assuntos
Fatores Imunológicos/administração & dosagem , Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/imunologia , Pinus/química , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Doenças das Aves Domésticas/imunologia , Própole/administração & dosagem , Animais , Vírus da Leucose Aviária/imunologia , Vírus da Leucose Aviária/fisiologia , Galinhas , Terapia de Imunossupressão , Doença de Newcastle/tratamento farmacológico , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/fisiologia , Pólen/química , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/virologia , Vírus da Reticuloendoteliose/imunologia , Vírus da Reticuloendoteliose/fisiologia , Vacinas Virais/administração & dosagemRESUMO
Newcastle disease (ND) is one of the highly pathogenic viral diseases of avian species. ND is economically significant because of the huge mortality and morbidity associated with it. The disease is endemic in many third world countries where agriculture serves as the primary source of national income. Newcastle disease virus (NDV) belongs to the family Paramyxoviridae and is well characterized member among the avian paramyxovirus serotypes. In recent years, NDV has lured the virologists not only because of its pathogenic potential, but also for its oncolytic activity and its use as a vaccine vector for both humans and animals. The NDV based recombinant vaccine offers a pertinent choice for the construction of live attenuated vaccine due to its modular nature of transcription, minimum recombination frequency, and lack of DNA phase during replication. Our current understanding about the NDV biology is expanding rapidly because of the availability of modern molecular biology tools and high-throughput complete genome sequencing.
Assuntos
Doenças das Aves/virologia , Vírus da Doença de Newcastle/fisiologia , Vírus Oncolíticos/fisiologia , Animais , Terapia Biológica/métodos , Aves , Portadores de Fármacos , Vetores Genéticos , Humanos , Vírus da Doença de Newcastle/genética , Vírus Oncolíticos/genéticaRESUMO
BACKGROUND: A limited number of studies have tested the effect of diets supplemented with black cumin seed (BCS) on the performance of laying hen. OBJECTIVE: To determine the effects of various levels of dietary BCS on the performance of laying hen. BIRDS AND METHODS: Three hundred 40-week-old rural Leghorn (White Leghorn males X F1 females of Fayoumi male X Rhode Island Red female) crossbred hens were randomly assigned to four groups with five replicates of 15 birds each (75 laying hens per group), and fed diets supplemented with 0%, 3%, 4% or 5% BCS for 60 days. Statistical analysis was performed by means of ANOVA. RESULTS: BCS at all levels revealed greater egg production, egg weight and egg mass than the control group. Similarly, feed conversion was improved by 0.50, 0.55 and 0.36 points compared to controls with the addition of 3%, 4% or 5% levels of BCS, respectively. Haugh units and yolk weights of eggs from hens that were fed diets containing 3%, 4% and 5% BCS were significantly greater than those from the control group. Supplementation of 4% or 5% BCS significantly increased shell thickness and decreased serum LDL cholesterol and egg yolk cholesterol concentration as compared to other groups. Mean hemagglutination inhibition titers against Newcastle disease virus were higher than in controls. CONCLUSION: BCS at levels of 4% or 5% positively influenced egg production, egg weight and shell quality. Furthermore, it decreased the concentration of serum LDL cholesterol and egg yolk cholesterol concentrations and enhanced immunity against Newcastle disease virus.
Assuntos
Galinhas/fisiologia , Suplementos Nutricionais/análise , Doença de Newcastle/imunologia , Nigella sativa/química , Óvulo/fisiologia , Doenças das Aves Domésticas/imunologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Anticorpos Antivirais/sangue , Relação Dose-Resposta a Droga , Gema de Ovo/química , Feminino , Imunidade Humoral , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/fisiologia , Óvulo/química , Óvulo/imunologia , Óvulo/virologia , Doenças das Aves Domésticas/virologia , Reprodução , Sementes/químicaRESUMO
Nuclear architecture as well as gene nuclear positioning can modulate gene expression. In this work, we have analyzed the nuclear position of the interferon-ß (IFN-ß) locus, responsible for the establishment of the innate antiviral response, with respect to pericentromeric heterochromatin (PCH) in correlation with virus-induced IFN-ß gene expression. Experiments were carried out in two different cell types either non-infected (NI) or during the time course of three different viral infections. In NI cells, we showed a monoallelic IFN-ß promoter association with PCH that strongly decreased after viral infection. Dissociation of the IFN-ß locus away from these repressive regions preceded strong promoter transcriptional activation and was reversible within 12 h after infection. No dissociation was observed after infection with a virus that abnormally maintained the IFN-ß gene in a repressed state. Dissociation induced after virus infection specifically targeted the IFN-ß locus without affecting the general structure and nuclear distribution of PCH clusters. Using cell lines stably transfected with wild-type or mutated IFN-ß promoters, we identified the proximal region of the IFN-ß promoter containing YY1 DNA-binding sites as the region regulating IFN-ß promoter association with PCH before as well as during virus infection.
Assuntos
Heterocromatina/química , Interferon beta/genética , Fator de Transcrição YY1/metabolismo , Animais , Sítios de Ligação , Linhagem Celular , DNA Satélite/análise , Camundongos , Vírus da Doença de Newcastle/fisiologia , Regiões Promotoras Genéticas , Vírus da Febre do Vale do Rift/fisiologia , Ativação TranscricionalRESUMO
Esculetin (6,7-dihydroxycoumarin) and its diacetate exhibited a marked inhibitory effect on Newcastle disease virus replication in cell cultures at concentrations of 36 microM and 62 microM, respectively. These compounds were selected from ten hydroxycoumarin derivatives through an in vitro antiviral screen involving viruses of the picorna-, orthomyxo-, paramyxo-, and herpes virus families.