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1.
Foodborne Pathog Dis ; 18(1): 24-30, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32716659

RESUMO

Norovirus is a major cause of foodborne disease and nonbacterial gastroenteritis globally. This study evaluated the antiviral effects of Magnolia officinalis extract and its honokiol and magnolol constituents against human norovirus surrogates, murine norovirus (MNV) and feline calicivirus (FCV) in vitro, and in model food systems. Pretreatment or cotreatment of M. officinalis extract at 1 mg/mL reduced MNV and FCV titers by 0.6-1.8 log. Honokiol and magnolol, which are the major polyphenols in the extract, showed significant antiviral effects against MNV and FCV. The virus-infected cells that were treated with M. officinalis extract exhibited significantly increased glutathione levels (p < 0.05). The extract, honokiol, and magnolol revealed ferric ion-reducing and 2,2-diphenyl-1-picrylhydrazyl radical scavenging activities in a dose-dependent manner. Furthermore, MNV and FCV titers were reduced by >1.6 log or to undetectable levels in apple, orange, and plum juices and by 0.9 and 1.6 log in milk, respectively, when they were treated with the extract at 5 mg/mL. Therefore, the present study suggests that M. officinalis extract can be used as an antiviral food material to control norovirus foodborne diseases.


Assuntos
Antivirais/farmacologia , Infecções por Caliciviridae/prevenção & controle , Magnolia , Norovirus/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Compostos de Bifenilo/farmacologia , Infecções por Caliciviridae/veterinária , Infecções por Caliciviridae/virologia , Calicivirus Felino/efeitos dos fármacos , Gatos , Doenças Transmitidas por Alimentos/veterinária , Doenças Transmitidas por Alimentos/virologia , Humanos , Lignanas/farmacologia , Camundongos
2.
J Appl Microbiol ; 128(6): 1534-1546, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31991509

RESUMO

AIMS: The objective was to evaluate the possible synergistic effect of cranberry juice (CJ) and commercial citrus extract (BS) against FCV-F9 viral titre in vitro in combination with γ-irradiation and to determinate the D10 values and radiosensitivity increase. METHODS AND RESULTS: Virus samples were treated with a formulation containing a mixture of BS or CJ. Results showed a D10 of 0·05, 0·42% and 1·34 kGy for the virus treated with the BS, the CJ and the irradiation alone respectively. Concentrations needed to reduce 6 log TCID50  ml-1 of viral titre were BS-0·3%, CJ-2·52% and 8·04 kGy. Irradiation combined with BS-0·01% and CJ-0·1% against FCV-F9 virus showed D10 values of 0·74 and 0·72 kGy, respectively, resulting in a viral radiosensitization of 1·28 and 1·50 for respective treatments. CONCLUSION: The higher viral radiosensitization observed after combining γ-irradiation with BS-0·01% and CJ-0·1% indicates that CJ and BS could be used as antiviral agents alone or in combination with γ-irradiation to prevent NoV outbreaks. SIGNIFICANCE AND IMPACT OF THE STUDY: Cranberry juice and BS could be used in hurdle approaches in combined treatment with γ-irradiation to assure food safety without a detrimental effect on nutritional value and maintain low processing cost.


Assuntos
Antivirais/farmacologia , Calicivirus Felino/fisiologia , Irradiação de Alimentos/métodos , Raios gama , Tolerância a Radiação/efeitos dos fármacos , Calicivirus Felino/efeitos dos fármacos , Calicivirus Felino/efeitos da radiação , Citrus/química , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Inocuidade dos Alimentos , Vaccinium macrocarpon/química
3.
J Antibiot (Tokyo) ; 72(12): 981-985, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31534199

RESUMO

Feline herpesvirus type 1 (FHV-1) causes a potentially fatal disease in cats. Through the use of virus inhibition and cytotoxicity assays, sinefungin, a nucleoside antibiotic, was assessed for its potential to inhibit the growth of FHV-1. Sinefungin inhibited in vitro growth of FHV-1 most significantly over other animal viruses, such as feline infectious peritonitis virus, equine herpesvirus, pseudorabies virus and feline calicivirus. Our results revealed that sinefungin specifically suppressed the replication of FHV-1 after its adsorption to the host feline kidney cells in a dose-dependent manner without obvious cytotoxicity to the host cells. This antibiotic can potentially offer a highly effective treatment for animals infected with FHV-1, providing alternative medication to currently available antiviral therapies.


Assuntos
Adenosina/análogos & derivados , Antivirais/farmacologia , Varicellovirus/efeitos dos fármacos , Adenosina/farmacologia , Adenosina/toxicidade , Animais , Antivirais/toxicidade , Calicivirus Felino/efeitos dos fármacos , Doenças do Gato/tratamento farmacológico , Gatos , Linhagem Celular , Coronavirus Felino/efeitos dos fármacos , Relação Dose-Resposta a Droga , Infecções por Herpesviridae/tratamento farmacológico , Infecções por Herpesviridae/veterinária , Herpesvirus Equídeo 1/efeitos dos fármacos , Herpesvirus Suídeo 1/efeitos dos fármacos , Cavalos , Rim/citologia , Rim/virologia , Testes de Toxicidade
4.
Viruses ; 11(6)2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151251

RESUMO

The widespread nature of calicivirus infections globally has a substantial impact on the health and well-being of humans and animals alike. Currently, the only vaccines approved against caliciviruses are for feline and rabbit-specific members of this group, and thus there is a growing effort towards the development of broad-spectrum antivirals for calicivirus infections. In this study, we evaluated the antiviral activity of the adenosine analogue NITD008 in vitro using three calicivirus model systems namely; feline calicivirus (FCV), murine norovirus (MNV), and the human norovirus replicon. We show that the nucleoside analogue (NA), NITD008, has limited toxicity and inhibits calicivirus replication in all three model systems with EC50 values of 0.94 µM, 0.91 µM, and 0.21 µM for MNV, FCV, and the Norwalk replicon, respectively. NITD008 has a similar level of potency to the most well-studied NA 2'-C-methylcytidine in vitro. Significantly, we also show that continual NITD008 treatment effectively cleared the Norwalk replicon from cells and treatment with 5 µM NITD008 was sufficient to completely prevent rebound. Given the potency displayed by NITD008 against several caliciviruses, we propose that this compound should be interrogated further to assess its effectiveness in vivo. In summary, we have added a potent NA to the current suite of antiviral compounds and provide a NA scaffold that could be further modified for therapeutic use against calicivirus infections.


Assuntos
Adenosina/análogos & derivados , Antivirais/farmacologia , Calicivirus Felino/efeitos dos fármacos , Norovirus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Adenosina/farmacologia , Animais , Infecções por Caliciviridae/tratamento farmacológico , Infecções por Caliciviridae/veterinária , Infecções por Caliciviridae/virologia , Gatos/virologia , Humanos , Nucleosídeos/farmacologia
5.
Food Microbiol ; 76: 346-353, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30166160

RESUMO

Plant polyphenols have shown antiviral activity against several human pathogens, but their physicochemical interactions are not well-understood. The objectives of this study were to compare the antiviral activity between monomeric catechin and dimeric procyanidin B2 (PB2) using cultivable human norovirus surrogates (feline calicivirus (FCV-F9) and murine norovirus (MNV-1)) and to understand their potential antiviral mechanism using virus-like particles (VLPs) and the P domain of human norovirus GII (HNoV GII.4). Surrogate viruses at 5 log PFU/mL were treated with 0.5-5 mg/mL monomeric catechin monohydrate, PB2 or phosphate buffered saline (PBS, pH 7.2; control) at 37 °C over 24 h. Infectivity was determined using plaque assays and data from triplicate experiments were statistically analyzed. PB2 at 0.5 mg/mL and 1 mg/mL reduced FCV-F9 to undetectable levels after 3 h and MNV-1 by 0.21 and 1.23 log PFU after 24 h, respectively. Monomeric catechins at 1 mg/mL reduced FCV-F9 to undetectable levels after 6 h and MNV-1 titers to undetectable levels after 24 h. In addition, PB2 was shown to directly bind the P domain, the main capsid structure of HNoVs in the ratio of 1:1 through spontaneous interactions. Electrostatic interactions played a dominant role between PB2 and the P domain. PB2 significantly altered tertiary but not secondary structures of VLPs. Transmission electron microscopy demonstrated that PB2 aggregated VLPs, further indicating interactions between them. These findings indicate that PB2 causes structural changes of the P domain of VLPs, mainly through direct interaction leading to HNoV inactivation.


Assuntos
Antivirais/farmacologia , Biflavonoides/farmacologia , Calicivirus Felino/efeitos dos fármacos , Catequina/farmacologia , Proantocianidinas/farmacologia , Inativação de Vírus/efeitos dos fármacos , Animais , Antivirais/metabolismo , Biflavonoides/metabolismo , Calicivirus Felino/metabolismo , Catequina/metabolismo , Gatos , Doenças Transmitidas por Alimentos/prevenção & controle , Humanos , Norovirus/efeitos dos fármacos , Proantocianidinas/metabolismo , Ensaio de Placa Viral , Ligação Viral
6.
Viruses ; 10(8)2018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-30115859

RESUMO

Feline calicivirus (FCV) is a major cause of upper respiratory tract disease in cats, with widespread distribution in the feline population. Recently, virulent systemic diseases caused by FCV infection has been associated with mortality rates up to 50%. Currently, there are no direct-acting antivirals approved for the treatment of FCV infection. Here, we tested 15 compounds from different antiviral classes against FCV using in vitro protein and cell culture assays. After the expression of FCV protease-polymerase protein, we established two in vitro assays to assess the inhibitory activity of compounds directly against the FCV protease or polymerase. Using this recombinant enzyme, we identified quercetagetin and PPNDS as inhibitors of FCV polymerase activity (IC50 values of 2.8 µM and 2.7 µM, respectively). We also demonstrate the inhibition of FCV protease activity by GC376 (IC50 of 18 µM). Using cell culture assays, PPNDS, quercetagetin and GC376 did not display antivirals effects, however, we identified nitazoxanide and 2'-C-methylcytidine (2CMC) as potent inhibitors of FCV replication, with EC50 values in the low micromolar range (0.6 µM and 2.5 µM, respectively). In conclusion, we established two in vitro assays that will accelerate the research for FCV antivirals and can be used for the high-throughput screening of direct-acting antivirals.


Assuntos
Antivirais/farmacologia , Calicivirus Felino/efeitos dos fármacos , Citidina/análogos & derivados , RNA Polimerases Dirigidas por DNA/antagonistas & inibidores , Peptídeo Hidrolases/metabolismo , Poliproteínas/antagonistas & inibidores , Tiazóis/farmacologia , Animais , Infecções por Caliciviridae/tratamento farmacológico , Infecções por Caliciviridae/veterinária , Infecções por Caliciviridae/virologia , Calicivirus Felino/genética , Calicivirus Felino/metabolismo , Doenças do Gato/tratamento farmacológico , Doenças do Gato/virologia , Gatos , Linhagem Celular , Citidina/farmacologia , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/virologia , Flavonas/farmacologia , Expressão Gênica , Ensaios de Triagem em Larga Escala , Concentração Inibidora 50 , Nitrocompostos , Peptídeo Hidrolases/genética , Poliproteínas/genética , Poliproteínas/metabolismo , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/veterinária , Infecções Respiratórias/virologia , Ácidos Sulfônicos/farmacologia
7.
PLoS One ; 12(5): e0176718, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28472060

RESUMO

Sanitation of environmental surfaces with chlorine based-disinfectants is a principal measure to control outbreaks of norovirus or Clostridium difficile. The microbicidal activity of chlorine-based disinfectants depends on the free available chlorine (FAC), but their oxidative potential is rapidly eliminated by organic matter. In this study, the microbicidal activities of weakly acidified chlorous acid water (WACAW) and sodium hypochlorite solution (NaClO) against feline calcivirus (FCV) and C. difficile spores were compared in protein-rich conditions. WACAW inactivated FCV and C. difficile spores better than NaClO under all experimental conditions used in this study. WACAW above 100 ppm FAC decreased FCV >4 log10 within 30 sec in the presence of 0.5% each of bovine serum albumin (BSA), polypeptone or meat extract. Even in the presence of 5% BSA, WACAW at 600 ppm FAC reduced FCV >4 log10 within 30 sec. Polypeptone inhibited the virucidal activity of WACAW against FCV more so than BSA or meat extract. WACAW at 200 ppm FAC decreased C. difficile spores >3 log10 within 1 min in the presence of 0.5% polypeptone. The microbicidal activity of NaClO was extensively diminished in the presence of organic matter. WACAW recovered its FAC to the initial level after partial neutralization by sodium thiosulfate, while no restoration of the FAC was observed in NaClO. These results indicate that WACAW is relatively stable under organic matter-rich conditions and therefore may be useful for treating environmental surfaces contaminated by human excretions.


Assuntos
Calicivirus Felino/efeitos dos fármacos , Cloretos/farmacologia , Clostridioides difficile/efeitos dos fármacos , Esporos Bacterianos/efeitos dos fármacos , Animais , Gatos , Clostridioides difficile/crescimento & desenvolvimento , Humanos , Ratos , Soroalbumina Bovina/metabolismo , Espectrofotometria Ultravioleta , Tiossulfatos/farmacologia
8.
Food Microbiol ; 63: 263-267, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28040178

RESUMO

Blueberry proanthocyanidins (B-PAC) are known to decrease titers of human norovirus surrogates in vitro. The application of B-PAC as therapeutic or preventive options against foodborne viral illness needs to be determined using model foods and simulated gastric conditions in vitro. The objective of this study was to evaluate the antiviral effect of B-PAC in model foods (apple juice (AJ) and 2% reduced fat milk) and simulated gastrointestinal fluids against cultivable human norovirus surrogates (feline calicivirus; FCV-F9 and murine norovirus; MNV-1) over 24 h at 37 °C. Equal amounts of each virus (5 log PFU/ml) was mixed with B-PAC (1, 2 and 5 mg/ml) prepared either in AJ, or 2% milk, or simulated gastric fluids and incubated over 24 h at 37 °C. Controls included phosphate buffered saline, malic acid (pH 7.2), AJ, 2% milk or simulated gastric and intestinal fluids incubated with virus over 24 h at 37 °C. The tested viruses were reduced to undetectable levels within 15 min with B-PAC (1, 2 and 5 mg/ml) in AJ (pH 3.6). However, antiviral activity of B-PAC was reduced in milk. FCV-F9 was reduced by 0.4 and 1.09 log PFU/ml with 2 and 5 mg/ml B-PAC in milk, respectively and MNV-1 titers were reduced by 0.81 log PFU/ml with 5 mg/ml B-PAC in milk after 24 h. B-PAC at 5 mg/ml in simulated intestinal fluid reduced titers of the tested viruses to undetectable levels within 30 min. Overall, these results show the potential of B-PAC as preventive and therapeutic options for foodborne viral illnesses.


Assuntos
Mirtilos Azuis (Planta)/química , Calicivirus Felino/crescimento & desenvolvimento , Norovirus/crescimento & desenvolvimento , Proantocianidinas/farmacologia , Animais , Antivirais/farmacologia , Calicivirus Felino/efeitos dos fármacos , Microbiologia de Alimentos , Doenças Transmitidas por Alimentos/prevenção & controle , Sucos de Frutas e Vegetais/análise , Sucos de Frutas e Vegetais/virologia , Ácido Gástrico/química , Trato Gastrointestinal/virologia , Humanos , Concentração de Íons de Hidrogênio , Leite/virologia , Norovirus/classificação , Norovirus/efeitos dos fármacos , Ensaio de Placa Viral , Inativação de Vírus , Vírus/efeitos dos fármacos
9.
Int J Biol Macromol ; 95: 160-167, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27865960

RESUMO

Inonotus obliquus polysaccharides (IOPs) are a potential drug for the prevention and treatment of cancer, cardiopathy, diabetes, AIDs, pancreatitis and other diseases. In this study, we found that IOP can act as a broad-spectrum antiviral drug against feline viruses in the in vitro experiment. Using cell models of feline calicivirus (FCV), we demonstrated that IOP treatment was capable of exhibiting anti-FCV strain F9 activity in cell-based assays and also showed low cytotoxicity. Investigation of the mechanism of action of the compound revealed that IOP treatment induces its inhibitory actions directly on virus particles through blocking viral binding/absorpting. The inhibitory activity against other FCV isolates from China was also identified. More importantly, we found that IOP exhibited broad-spectrum antiviral activity against the feline herpesvirus 1, feline influenza virus H3N2 and H5N6, feline panleukopenia virus and feline infectious peritonitis virus that can contribute to respiratory and gastrointestinal diseases in cats. These findings suggest that IOP may be a potential broad-spectrum antiviral drug against feline viruses.


Assuntos
Antivirais/farmacologia , Basidiomycota/química , Calicivirus Felino/efeitos dos fármacos , Polissacarídeos Fúngicos/farmacologia , Animais , Antivirais/química , Antivirais/isolamento & purificação , Calicivirus Felino/fisiologia , Gatos , Relação Dose-Resposta a Droga , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/isolamento & purificação , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
10.
Biosci Biotechnol Biochem ; 80(6): 1196-204, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26983677

RESUMO

Black raspberry seeds, a byproduct of wine and juice production, contain large quantities of polyphenolic compounds. The antiviral effects of black raspberry seed extract (RCS) and its fraction with molecular weight less than 1 kDa (RCS-F1) were examined against food-borne viral surrogates, murine norovirus-1 (MNV-1) and feline calicivirus-F9 (FCV-F9). The maximal antiviral effect was achieved when RCS or RCS-F1 was added simultaneously to cells with MNV-1 or FCV-F9, reaching complete inhibition at 0.1-1 mg/mL. Transmission electron microscopy (TEM) images showed enlarged viral capsids or disruption (from 35 nm to up to 100 nm) by RCS-F1. Our results thus suggest that RCS-F1 can interfere with the attachment of viral surface protein to host cells. Further, two polyphenolic compounds derived from RCS-F1, cyanidin-3-glucoside (C3G) and gallic acid, identified by liquid chromatography-tandem mass spectrometry, showed inhibitory effects against the viruses. C3G was suggested to bind to MNV-1 RNA polymerase and to enlarge viral capsids using differential scanning fluorimetry and TEM, respectively.


Assuntos
Antivirais/farmacologia , Calicivirus Felino/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Norovirus/efeitos dos fármacos , Rubus/química , Proteínas Virais/antagonistas & inibidores , Animais , Antivirais/isolamento & purificação , Calicivirus Felino/genética , Calicivirus Felino/crescimento & desenvolvimento , Catequina/isolamento & purificação , Catequina/farmacologia , Gatos , Ácido Elágico/isolamento & purificação , Ácido Elágico/farmacologia , Células Epiteliais/virologia , Ácido Gálico/isolamento & purificação , Ácido Gálico/farmacologia , Expressão Gênica , Rim/efeitos dos fármacos , Rim/virologia , Camundongos , Norovirus/genética , Norovirus/crescimento & desenvolvimento , Extratos Vegetais/química , Sementes/química , Proteínas Virais/genética , Proteínas Virais/metabolismo
11.
Infect Control Hosp Epidemiol ; 37(5): 561-6, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26861195

RESUMO

OBJECTIVE: To determine whether hydrogen peroxide vapor (HPV) could be used to decontaminate caliciviruses from surfaces in a patient room. DESIGN: Feline calicivirus (FCV) and murine norovirus (MNV) were used as surrogate viability markers to mimic the noncultivable human norovirus. Cell culture supernatants of FCV and MNV were dried in triplicate 35-mm wells of 6-well plastic plates. These plates were placed in various positions in a nonoccupied patient room that was subsequently exposed to HPV. Control plates were positioned in a similar room but were never exposed to HPV. METHODS: Virucidal activity was measured in cell culture by reduction in 50% tissue culture infective dose titer for FCV and by both 50% tissue culture infective dose titer and plaque reduction for MNV. RESULTS: Neither viable FCV nor viable MNV could be detected in the test room after HPV treatment. At least 3.65 log reduction for FCV and at least 3.67 log reduction for MNV were found by 50% tissue culture infective dose. With plaque assay, measurable reduction for MNV was at least 2.85 log units. CONCLUSIONS: The successful inactivation of both surrogate viruses indicates that HPV could be a useful tool for surface decontamination of a patient room contaminated by norovirus. Hence nosocomial spread to subsequent patients can be avoided.


Assuntos
Anti-Infecciosos Locais/farmacologia , Calicivirus Felino/efeitos dos fármacos , Infecção Hospitalar/prevenção & controle , Descontaminação/métodos , Peróxido de Hidrogênio/farmacologia , Norovirus/efeitos dos fármacos , Animais , Gatos , Linhagem Celular , Humanos , Camundongos , Quartos de Pacientes/normas , Células RAW 264.7
12.
J Virol ; 89(9): 4942-50, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25694593

RESUMO

UNLABELLED: Feline infectious peritonitis and virulent, systemic calicivirus infection are caused by certain types of feline coronaviruses (FCoVs) and feline caliciviruses (FCVs), respectively, and are important infectious diseases with high fatality rates in members of the Felidae family. While FCoV and FCV belong to two distinct virus families, the Coronaviridae and the Caliciviridae, respectively, they share a dependence on viral 3C-like protease (3CLpro) for their replication. Since 3CLpro is functionally and structurally conserved among these viruses and essential for viral replication, 3CLpro is considered a potential target for the design of antiviral drugs with broad-spectrum activities against these distinct and highly important viral infections. However, small-molecule inhibitors against the 3CLpro enzymes of FCoV and FCV have not been previously identified. In this study, derivatives of peptidyl compounds targeting 3CLpro were synthesized and evaluated for their activities against FCoV and FCV. The structures of compounds that showed potent dual antiviral activities with a wide margin of safety were identified and are discussed. Furthermore, the in vivo efficacy of 3CLpro inhibitors was evaluated using a mouse model of coronavirus infection. Intraperitoneal administration of two 3CLpro inhibitors in mice infected with murine hepatitis virus A59, a hepatotropic coronavirus, resulted in significant reductions in virus titers and pathological lesions in the liver compared to the findings for the controls. These results suggest that the series of 3CLpro inhibitors described here may have the potential to be further developed as therapeutic agents against these important viruses in domestic and wild cats. This study provides important insights into the structure and function relationships of 3CLpro for the design of antiviral drugs with broader antiviral activities. IMPORTANCE: Feline infectious peritonitis virus (FIPV) is the leading cause of death in young cats, and virulent, systemic feline calicivirus (vs-FCV) causes a highly fatal disease in cats for which no preventive or therapeutic measure is available. The genomes of these distinct viruses, which belong to different virus families, encode a structurally and functionally conserved 3C-like protease (3CLpro) which is a potential target for broad-spectrum antiviral drug development. However, no studies have previously reported a structural platform for the design of antiviral drugs with activities against these viruses or on the efficacy of 3CLpro inhibitors against coronavirus infection in experimental animals. In this study, we explored the structure-activity relationships of the derivatives of 3CLpro inhibitors and identified inhibitors with potent dual activities against these viruses. In addition, the efficacy of the 3CLpro inhibitors was demonstrated in mice infected with a murine coronavirus. Overall, our study provides the first insight into a structural platform for anti-FIPV and anti-FCV drug development.


Assuntos
Antivirais/isolamento & purificação , Calicivirus Felino/enzimologia , Coronavirus Felino/enzimologia , Inibidores de Proteases/isolamento & purificação , Proteínas Virais/antagonistas & inibidores , Proteases Virais 3C , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Calicivirus Felino/efeitos dos fármacos , Gatos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Coronavirus Felino/efeitos dos fármacos , Cisteína Endopeptidases , Modelos Animais de Doenças , Feminino , Fígado/patologia , Camundongos Endogâmicos BALB C , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico , Resultado do Tratamento
13.
Bioorg Med Chem ; 22(11): 2974-83, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24775916

RESUMO

A synthetic route toward a series of unique cyclic nucleoside phosphonates locked in South conformation is described. The desired conformation is stabilized by a substitution of the sugar moiety by bicyclo[2.2.1]heptane (norbornane) bearing a purine or pyrimidine nucleobase in the bridgehead position. Although the final phosphonate derivatives are devoid of any significant antiviral activity probably due to the unfavorable conformational properties, several intermediates and their analogs exhibit surprising activity against feline herpes virus. Since these compounds do not possess an appropriate hydroxymethyl function allowing phosphorylation and subsequent incorporation into the polynucleotide chain, it seems to be likely that these compounds act by a novel unknown mechanism of action and may represent a new possible alternative for nucleoside and nucleotide therapeutics of this widely spread feline infection. A number of derivatives exerted also a significant antiviral activity against Coxsackievirus B3 and B4.


Assuntos
Antivirais/farmacologia , Calicivirus Felino/efeitos dos fármacos , Norbornanos/farmacologia , Nucleotídeos/farmacologia , Antivirais/síntese química , Antivirais/química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Norbornanos/síntese química , Norbornanos/química , Nucleotídeos/síntese química , Nucleotídeos/química , Relação Estrutura-Atividade
14.
Foodborne Pathog Dis ; 11(3): 224-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24350883

RESUMO

Norovirus infection is a major cause of nonbacterial foodborne outbreaks worldwide, but no specific treatments are available yet. In this study, we investigated the antiviral activity of mulberry (Morus alba, Ma) juice and its fractions on murine norovirus-1 (MNV-1) and feline calicivirus-F9 (FCV-F9) as human norovirus surrogates using cytopathic effect inhibition, plaque reduction, and RNA expression assays. In time-of-addition experiments, Ma juice was found to be effective in reducing the infectivity of MNV-1 and FCV-F9 in the pre- and co-treatments. The effective concentration for 50% reduction was approximately 0.005% juice (relative to 100% natural juice) and 0.25% juice for MNV-1 and FCV-F9, respectively. Ma juice at 0.1% exhibited about 60% reduction of the MNV-1 polymerase gene expression, confirming the inhibition of viral replication. In an attempt to identify active components with antiviral activities, Ma-F1 (<3 kDa) and Ma-F2 (>3 kDa) were examined to show that Ma-F2 was more effective than Ma-F1 in all modes, except for pre-virus treatment. Nevertheless, two major polyphenolic compounds of Ma juice, cyanidin-3-glucoside and cyanidin-3-rutinoside, showed antiviral activity in the co-treatment mode. Our results suggest that Ma juice and its fractions may inhibit internalization and replication of MNV-1, whereas it may influence adherence or internalization of FCV-F9 virions. Ma juice may prove useful in the prevention of foodborne viral infection.


Assuntos
Antivirais/farmacologia , Bebidas , Infecções por Caliciviridae/prevenção & controle , Calicivirus Felino/efeitos dos fármacos , Doenças Transmitidas por Alimentos/prevenção & controle , Morus/química , Norovirus/efeitos dos fármacos , Animais , Antocianinas/farmacologia , Infecções por Caliciviridae/virologia , Gatos , Linhagem Celular , Doenças Transmitidas por Alimentos/virologia , Glucosídeos/farmacologia , Humanos , Camundongos , Ensaio de Placa Viral , Inativação de Vírus/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos
15.
Yakugaku Zasshi ; 133(9): 1017-22, 2013.
Artigo em Japonês | MEDLINE | ID: mdl-23995810

RESUMO

Noroviruses are one of the most important causes of acute gastroenteritis throughout the world. The aim of this study is to evaluate the efficacy of a chlorine dioxide gas-generating gel (ClO2 gel, 60 g) against feline calicivirus (FCV), a norovirus surrogate, in the wet state on glass dishes in a test sink (43 cm long, 75 cm wide, and 29 cm deep). The ClO2 gel permits sustained release of gaseous ClO2 (1.7 mg/h at 25°C), and was placed in one corner of the test sink. The glass dishes containing FCV suspension were placed at three positions in the test sink. We demonstrated that FCV was inactivated within 5h (>2 or >3 log10 reductions at three positions, n=20) in the test sink where the ClO2 gel was placed. These small quantities of ClO2 gel might be a useful tool for reducing the risk of infection by norovirus in wet environments such as kitchens and bathrooms under optimal condition.


Assuntos
Calicivirus Felino/efeitos dos fármacos , Compostos Clorados/farmacologia , Óxidos/farmacologia , Gases , Géis , Norovirus/efeitos dos fármacos , Inativação de Vírus
16.
Foodborne Pathog Dis ; 9(10): 915-21, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22924523

RESUMO

Abstract Human noroviruses (HuNoVs) are the most frequent cause of foodborne viral gastroenteritis, causing approximately 90% of non-bacterial epidemic outbreaks around the world. Rubus coreanus is a species of black raspberry, rich in polyphenols, and known to exert anti-inflammatory, antibacterial, and antiviral activities. In the present study, the antiviral effects of R. coreanus juice (black raspberry [BRB] juice) on foodborne viral surrogates, murine norovirus-1 (MNV-1) and feline calicivirus-F9 (FCV-F9), were compared with those of cranberry juice, grape juice, and orange juice by plaque assays. Among the four juices tested, BRB juice was the most effective in reducing plaques formation of these viruses. Time-of-addition experiments were designed to determine the mechanism of action of BRB juice on MNV-1 and FCV-F9. The maximal antiviral effect of BRB juice against MNV-1 was observed when it was added to RAW 264.7 cells (mouse leukemic monocyte macrophage cell line) simultaneously with the virus. Pre-treatment of either Crandell Reese Feline Kidney cells or FCV-F9 with BRB juice exhibited significant antiviral activity. The inhibition of viral infection by BRB juice on MNV-1 and FCV-F9 probably occurs at the internalization of virions into the cell or the attachment of the viral surface protein to the cellular receptor. The polyphenol components in BRB (i.e., gallic acid and quercetin), however, did not show any activity against these viruses. Our data provide great promise for the utilization of BRB in the prevention of foodborne viral outbreaks.


Assuntos
Antivirais/farmacologia , Calicivirus Felino/efeitos dos fármacos , Doenças Transmitidas por Alimentos/tratamento farmacológico , Norovirus/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rosaceae/química , Animais , Bebidas , Calicivirus Felino/crescimento & desenvolvimento , Gatos , Linhagem Celular , Citrus sinensis/química , Contaminação de Alimentos , Manipulação de Alimentos/métodos , Microbiologia de Alimentos , Ácido Gálico/farmacologia , Camundongos , Norovirus/crescimento & desenvolvimento , Polifenóis/farmacologia , Quercetina/farmacologia , Replicação Viral , Vitis/química
17.
Lett Appl Microbiol ; 53(6): 628-34, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21950421

RESUMO

AIMS: To evaluate the efficacy of low-concentration chlorine dioxide (ClO(2)) gas against model microbes in the wet state on a glass surface. METHODS AND RESULTS: We set up a test room (39 m(3)) and the ClO(2) gas was produced by a ClO(2) gas generator that continuously releases a constant low-concentration ClO(2) gas. Influenza A virus (Flu-A), feline calicivirus (FCV), Staphylococcus aureus and Escherichia coli were chosen as the model microbes. The low-concentration ClO(2) gas (mean 0.05 ppmv, 0.14 mg m(-3)) inactivated Flu-A and E. coli (>5 log(10) reductions) and FCV and S. aureus (>2 log(10) reductions) in the wet state on glass dishes within 5 h. CONCLUSIONS: The treatment of wet environments in the presence of human activity such as kitchens and bathrooms with the low-concentration ClO(2) gas would be useful for reducing the risk of infection by bacteria and viruses residing on the environmental hard surfaces without adverse effects. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates that the low-concentration ClO(2) gas (mean 0.05 ppmv) inactivates various kinds of microbes such as Gram-positive and Gram-negative bacteria, enveloped and nonenveloped viruses in the wet state.


Assuntos
Bactérias/efeitos dos fármacos , Compostos Clorados/farmacologia , Desinfetantes/farmacologia , Vidro , Óxidos/farmacologia , Vírus/efeitos dos fármacos , Microbiologia da Água , Animais , Calicivirus Felino/efeitos dos fármacos , Gatos , Escherichia coli/efeitos dos fármacos , Humanos , Vírus da Influenza A/efeitos dos fármacos , Staphylococcus aureus/metabolismo
18.
Foodborne Pathog Dis ; 8(11): 1177-83, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21777065

RESUMO

Pomegranate juice (PJ) and pomegranate polyphenolic extracts (PP) have antiviral effects against HIV-1, influenza, herpes, and poxviruses, and we recently demonstrated their effect against human noroviral surrogates. In the present study, the time-dependent effects of two commercial brands of PJ and PP at two concentrations (2 and 4 mg/mL) on the infectivity of foodborne viral surrogates (feline calicivirus FCV-F9, murine norovirus MNV-1, and MS2 bacteriophage) at room temperature for up to 1 h were evaluated. Each virus at ∼5 log(10) plaque-forming units (PFU)/mL was mixed with equal volumes of PJ, or PP at 4 or 8 mg/mL, and incubated for 0, 10, 20, 30, 45, and 60 min at room temperature. Viral titers after each treatment were determined by standardized plaque assays and compared with untreated controls. Virus titer reduction by PJ and PP was found to be a rather rapid process, with ≥50% of titer reduction occurring within the first 20 min of treatment for all three tested viruses. Within the first 20 min, titer reductions of 3.12, 0.79, and 0.23 log(10) PFU/mL for FCV-F9, MNV-1, and MS2, respectively, were obtained using PJ. FCV-F9, MNV-1, and MS2 titers were reduced by 4.02, 0.68, and 0.18 log(10) PFU/mL with 2 mg/mL PP and 5.09, 1.14, and 0.19 log(10) PFU/mL with 4 mg/mL PP, respectively, after 20 min. The mechanism of viral reduction by PJ and PP needs to be elucidated and clinical trials should be undertaken before recommending for therapeutic or preventive purposes.


Assuntos
Antivirais/farmacologia , Bebidas , Calicivirus Felino/efeitos dos fármacos , Lythraceae/química , Norovirus/efeitos dos fármacos , Polifenóis/farmacologia , Animais , Calicivirus Felino/patogenicidade , Gatos , Linhagem Celular , Escherichia coli , Doenças Transmitidas por Alimentos/prevenção & controle , Doenças Transmitidas por Alimentos/virologia , Humanos , Concentração de Íons de Hidrogênio , Levivirus/efeitos dos fármacos , Levivirus/patogenicidade , Camundongos , Norovirus/patogenicidade , Fatores de Tempo , Carga Viral , Ensaio de Placa Viral
19.
Foodborne Pathog Dis ; 8(9): 1005-10, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21457050

RESUMO

Free chlorine as hypochlorite is recommended to decontaminate fecally contaminated surfaces to control human norovirus (NoV). We evaluated the efficacy of sodium hypochlorite to decontaminate GII.4 NoV and three surrogates of human NoVs, feline calicivirus (FCV), murine norovirus (MNV), and coliphage MS2, on a fecally soiled stainless steel surface. Reduction of infectivity of FCV, MNV, and MS2 was measured by plaque assay and the decline of genomic copy numbers of GII.4 NoV by reverse transcriptase-polymerase chain reaction. Sodium hypochlorite solution at 5000 ppm could inactivate FCV by 3 log(10) plaque forming units after approximately 1.9 minutes of contact time, but required longer exposure times of 3.2 and 4.5 minutes to reduce MNV and MS2 by 3 log(10), respectively. However, detection of viral RNA by reverse transcriptase-polymerase chain reaction assay may not be reliable to estimate the effectiveness of sodium hypochlorite against human NoV. Of three NoV surrogates, FCV is not the most resistant of the virus tested for inactivation by hypochlorite and thus is not the worst-case model for estimating NoV inactivation. Although the use of 5000 ppm of hypochlorite for fecally soiled surfaces is effective, it may require longer exposure times of ≥3 minutes to control NoVs. Surface precleaning before hypochlorite disinfection is recommended to initially reduce the fecal organic load for better virus inactivation and should be a part of the environmental hygiene response measures during an NoV outbreak or where NoV fecal contamination of environmental surfaces is likely or suspected to be present.


Assuntos
Antivirais/farmacologia , Calicivirus Felino/efeitos dos fármacos , Desinfetantes/farmacologia , Fezes/virologia , Leviviridae/efeitos dos fármacos , Norovirus/efeitos dos fármacos , Hipoclorito de Sódio/farmacologia , Calicivirus Felino/crescimento & desenvolvimento , Calicivirus Felino/isolamento & purificação , Calicivirus Felino/patogenicidade , Farmacorresistência Viral , Microbiologia Ambiental , Dosagem de Genes , Humanos , Cinética , Leviviridae/crescimento & desenvolvimento , Leviviridae/isolamento & purificação , Leviviridae/patogenicidade , Levivirus/efeitos dos fármacos , Levivirus/crescimento & desenvolvimento , Levivirus/isolamento & purificação , Levivirus/patogenicidade , Norovirus/genética , Norovirus/isolamento & purificação , Norovirus/patogenicidade , Concentração Osmolar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Aço Inoxidável , Propriedades de Superfície , Ensaio de Placa Viral , Virologia/métodos , Inativação de Vírus/efeitos dos fármacos
20.
Biocontrol Sci ; 15(2): 45-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20616431

RESUMO

We evaluated the antiviral activity of a chlorine dioxide gas solution (CD) and sodium hypochlorite (SH) against feline calicivirus, human influenza virus, measles virus, canine distemper virus, human herpesvirus, human adenovirus, canine adenovirus and canine parvovirus. CD at concentrations ranging from 1 to 100 ppm produced potent antiviral activity, inactivating >or= 99.9% of the viruses with a 15 sec treatment for sensitization. The antiviral activity of CD was approximately 10 times higher than that of SH.


Assuntos
Antivirais/farmacologia , Compostos Clorados/farmacologia , Óxidos/farmacologia , Hipoclorito de Sódio/farmacologia , Adenovirus Caninos/efeitos dos fármacos , Adenovírus Humanos/efeitos dos fármacos , Calicivirus Felino/efeitos dos fármacos , Vírus da Cinomose Canina/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Vírus do Sarampo/efeitos dos fármacos , Orthomyxoviridae/efeitos dos fármacos , Parvovirus Canino/efeitos dos fármacos
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