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1.
PLoS One ; 14(5): e0216875, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091273

RESUMO

Gastroretentive (GR) systems are designed to prolong gastric residence time to allow sustained absorption and improve the oral bioavailability of drugs with a narrow absorption window in the upper part of the gastrointestinal tract. The present study aimed to develop a GR system for acyclovir using 3D printing technology and evaluate its in vivo pharmacokinetics after oral administration in Beagle dogs. The system consisted of a gastro-floating device, which can float in the gastric fluid, prepared by a fused deposition modeling 3D printer and conventional acyclovir sustained-release (SR) tablet. The acyclovir SR tablet was inserted to the floating device to allow sustained release of the drug in the stomach. The buoyancy and sustained-release property of the developed GR system were determined using an in vitro dissolution test, in vivo pharmacokinetic study, and abdominal X-ray imaging in Beagle dogs. The in vivo dissolution profiles of the GR system were also predicted based on the in vivo pharmacokinetic data using a population pharmacokinetic (POP-PK) model. In the dissolution test, the sustained-release characteristic of the GR system was identified with a time corresponding to 80% dissolution (T80) of 2.52 h. Following oral administration of the GR system, the time to reach the maximum concentration (Tmax) of acyclovir was significantly prolonged, whereas the maximum concentration (Cmax) decreased and the area under the curve increased compared with those obtained after the administration of immediate-release and SR tablets, indicating prolonged absorption. By X-ray imaging, we showed that the developed GR system stayed in the stomach for more than 12 h. The POP-PK model successfully described the observed plasma concentration-time data and predicted the in vivo biphasic dissolution profiles of the GR system, which was significantly different from the in vitro dissolution. The developed GR system could be applied to various drugs and had great prospects in the design and development of novel controlled-release formulations.


Assuntos
Aciclovir , Impressão Tridimensional , Aciclovir/química , Aciclovir/farmacocinética , Aciclovir/farmacologia , Administração Oral , Animais , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Cães , Avaliação Pré-Clínica de Medicamentos , Feminino , Masculino , Comprimidos
2.
mBio ; 10(3)2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088925

RESUMO

Viruses commandeer host cell 26S proteasome activity to promote viral entry, gene expression, replication, assembly, and egress. Proteasomal degradation activity is critical for herpes simplex virus (HSV) infection. The proteasome inhibitor bortezomib (also known as Velcade and PS-341) is a clinically effective antineoplastic drug that is FDA approved for treatment of hematologic malignancies such as multiple myeloma and mantle cell lymphoma. Low nanomolar concentrations of bortezomib inhibited infection by HSV-1, HSV-2, and acyclovir-resistant strains. Inhibition coincided with minimal cytotoxicity. Bortezomib did not affect attachment of HSV to cells or inactivate the virus directly. Bortezomib acted early in HSV infection by perturbing two distinct proteasome-dependent steps that occur within the initial hours of infection: the transport of incoming viral nucleocapsids to the nucleus and the virus-induced disruption of host nuclear domain 10 (ND10) structures. The combination of bortezomib with acyclovir demonstrated synergistic inhibitory effects on HSV infection. Thus, bortezomib is a novel potential therapeutic for HSV with a defined mechanism of action.IMPORTANCE Viruses usurp host cell functions to advance their replicative agenda. HSV relies on cellular proteasome activity for successful infection. Proteasome inhibitors, such as MG132, block HSV infection at multiple stages of the infectious cycle. Targeting host cell processes for antiviral intervention is an unconventional approach that might limit antiviral resistance. Here we demonstrated that the proteasome inhibitor bortezomib, which is a clinically effective cancer drug, has the in vitro features of a promising anti-HSV therapeutic. Bortezomib inhibited HSV infection during the first hours of infection at nanomolar concentrations that were minimally cytotoxic. The mechanism of bortezomib's inhibition of early HSV infection was to halt nucleocapsid transport to the nucleus and to stabilize the ND10 cellular defense complex. Bortezomib and acyclovir acted synergistically to inhibit HSV infection. Overall, we present evidence for the repurposing of bortezomib as a novel antiherpesviral agent and describe specific mechanisms of action.


Assuntos
Antivirais/farmacologia , Bortezomib/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Inibidores de Proteassoma/farmacologia , Internalização do Vírus/efeitos dos fármacos , Aciclovir/farmacologia , Animais , Núcleo Celular/metabolismo , Sinergismo Farmacológico , Fibroblastos/efeitos dos fármacos , Fibroblastos/virologia , Prepúcio do Pênis/citologia , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 2/fisiologia , Humanos , Masculino , Nucleocapsídeo/metabolismo , Células Vero
3.
Cell Mol Biol (Noisy-le-grand) ; 65(3): 66-71, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30942157

RESUMO

Human cytomegalovirus (HCMV) is a beta herpesvirus which large amount of people in world has interacted with. Recent studies indicated that CMV DNA is associated with several cancer types including "Glioblastoma (GBM)" which is the most common and aggressive type of primary brain cancer. In clinical studies it was shown that several antiviral medicines prolonged life span of glioblastoma patients. One of them is Acyclovir (ACV) which is a type of nucleoside analog, used to cure viral infections and might be a potential treatment supplement for Glioblastoma. In this study we aimed to investigate if ACV had cytotoxic effect on glioblastoma cell line U87 MG and also the effect of ACV on healthy cells. Furthermore it was aimed to search the effect of Rosmarinus Officinalis also known as rosemary which is an aromatic, perennial plant concurrent with ACV on glioblastoma and healthy cells.


Assuntos
Aciclovir/uso terapêutico , Glioblastoma/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Rosmarinus/química , Aciclovir/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Camundongos , Extratos Vegetais/farmacologia , Survivina/genética , Survivina/metabolismo , Células Tumorais Cultivadas
4.
Complement Ther Med ; 43: 81-84, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30935560

RESUMO

OBJECTIVES: To assess the value of bee products with respect to antiviral efficacy against herpes viruses. DESIGN: A systematic review was done using the JUSTfind System of the Justus-Liebig-University Gießen and Scopus. RESULTS: Three trials on honey and 6 trials on propolis were conducted. Each trial provided evidence that these two bee products are interesting alternatives to acyclovir, especially propolis, which was found to be superior to acyclovir in 4 trials. CONCLUSIONS: The evidence from these trials suggests that propolis is the best of all natural possibilities in the treatment of herpetic skin lesions, especially those related to HSV-1. Future studies should analyse if propolis could be an adjunct to treatment with acyclovir. For lesions in the oral cavity, honey could be an interesting alternative.


Assuntos
Antivirais/farmacologia , Abelhas/metabolismo , Vesícula/tratamento farmacológico , Genitália/efeitos dos fármacos , Boca/efeitos dos fármacos , Simplexvirus/efeitos dos fármacos , Pele/efeitos dos fármacos , Aciclovir/farmacologia , Animais , Vesícula/virologia , Genitália/virologia , Humanos , Boca/virologia , Própole/farmacologia , Pele/virologia
5.
Virol Sin ; 34(3): 315-323, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30915606

RESUMO

Honokiol is a pleiotropic natural compound isolated from Magnolia and has multiple biological and clinically relevant effects, including anticancer and antimicrobial function. However, the antiviral activity of honokiol has not yet been well studied. Here we showed that honokiol had no effect on herpes simplex virus-1 (HSV-1) entry, but inhibited HSV-1 viral DNA replication, gene expression and the production of new progeny viruses. The combination of honokiol and clinical drug acyclovir augmented inhibition of HSV-1 infection. Our results illustrate that honokiol could be a potential new candidate for clinical consideration in the treatment of HSV-1 infection alone or combination with other therapeutics.


Assuntos
Antivirais/farmacologia , Compostos de Bifenilo/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Lignanas/farmacologia , Replicação Viral/efeitos dos fármacos , Aciclovir/farmacologia , Animais , Replicação do DNA , Genoma Viral , Herpesvirus Humano 1/fisiologia , Magnolia/química , Camundongos , Camundongos Endogâmicos C57BL , Compostos Fitoquímicos/farmacologia , Células Vero
7.
Arch Virol ; 164(5): 1259-1269, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30903291

RESUMO

The long-term administration of acyclovir (ACV) for therapy against herpes simplex virus type 1 (HSV-1) infections can result in the emergence of ACV-resistant HSV strains. It is therefore urgent to develop new anti-herpetic compounds with mechanisms that differ from that of ACV. Cyanovirin-N (CV-N) is an antiviral agent that has an inhibitory effect on HSV-1 infections, and PEGylation of CV-N is potentially useful for pharmaceutical applications. Here, a (Gly4Ser)3 linker molecule was attached to the N-terminus of CV-N, and the resulting compound, linker-CV-N (LCV-N), was produced on a pilot scale with purity up to 95%. Then, PEG10k-LCV-N was synthesized by modifying at the α-amine group of the N-terminus of LCV-N with 10-kDa polyethylene glycol propionaldehyde (mPEG-ALD). CV-N, LCV-N and PEG10k-LCV-N were all found to have potent inhibitory activity against ACV-resistant HSV strains with IC50 values in the nM range. LCV-N was the most potent of these three compounds against both normal and ACV-resistant HSV strains. Although PEG10k-LCV-N showed less antiviral activity than CV-N and LCV-N, it still exhibited significant and universal virucidal activity against drug-resistant viruses. The toxicity and immunogenicity of PEG10k-LCV-N were dramatically lower than those of CV-N and LCV-N. In conclusion, we suggest that LCV-N and PEG10k-LCV-N are promising and safe microbicides for the control and/or treatment of ACV-resistant HSV infection.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/uso terapêutico , Proteínas de Transporte/química , Proteínas de Transporte/uso terapêutico , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Polietilenoglicóis/química , Aciclovir/farmacologia , Animais , Proteínas de Bactérias/síntese química , Proteínas de Transporte/síntese química , Linhagem Celular , Farmacorresistência Viral/genética , Feminino , Herpesvirus Humano 1/crescimento & desenvolvimento , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Sprague-Dawley , Células Vero
8.
Bioorg Med Chem ; 27(6): 1023-1033, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30738653

RESUMO

A series of tricyclic penciclovir (PCV) and hydroxybutylguanine (HBG) derivatives have been prepared with enhanced lipophilicity following an efficient synthetic route. All the novel tricyclic derivatives were evaluated for inhibitory activity against herpes simplex virus 1 and 2 (HSV-1, HSV-2) and thymidine kinase deficient (ACV resistant) HSV-1. The tricyclic HBG derivatives were devoid of inhibitory activity however several of the tricyclic PCV derivatives showed promising antiviral activity, in particular 9g (R = 4-MeO-C6H4) displayed good inhibitory activity (HSV-1 EC50 1.5 µM, HSV-2 EC50 0.8 µM) and retained inhibitory activity in HSV-1 TK- cells (EC50 0.8 µM). Computational docking experiments supported the biological data observed and this preliminary study provides useful data for further development of tricyclic acyclic nucleoside derivatives with improved lipophilicity and retention of activity in HSV-1 TK deficient strains. Also, the new tricyclic derivatives were evaluated against a broad range of other DNA and RNA viruses, but were found to be inactive at subtoxic concentrations. In addition, weak to moderate cytostatic effect was observed for the new compounds.


Assuntos
Aciclovir/análogos & derivados , Antivirais/química , Antivirais/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Aciclovir/síntese química , Aciclovir/química , Aciclovir/farmacologia , Antivirais/síntese química , Guanina/análogos & derivados , Guanina/síntese química , Guanina/farmacologia , Herpes Genital/tratamento farmacológico , Herpes Simples/tratamento farmacológico , Humanos , Modelos Moleculares
9.
Clin Respir J ; 13(3): 189-191, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30666793

RESUMO

BACKGROUND: Disseminated herpes zoster infection occurs mostly in immunocompromised hosts. There have been recent reports of disseminated zoster with chemotherapeutic regimens and newer monoclonal antibodies. CASE REPORT: The present case describes a 61-year-old patient presenting with disseminated herpes zoster after initiation of benralizumab, an anti-IL-5 monoclonal antibody for severe persistent asthma. His initial vesicular lesions limited to left lumbar dermatomes progressed extensively resulting in dissemination on his body. The diagnosis was confirmed with PCR and he had remarkable clinical improvement with acyclovir and supportive medical management. CONCLUSION: Clinical trials have reported an association of mepolizumab, another anti-IL-5 monoclonal antibody with herpes zoster. This report of herpes zoster following initiation of benralizumab might suggest a possibility of a class effect of anti-IL-5 monoclonal antibody.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Asma/tratamento farmacológico , Herpes Zoster/induzido quimicamente , Aciclovir/farmacologia , Aciclovir/uso terapêutico , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 3/efeitos dos fármacos , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/isolamento & purificação , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
10.
Mar Drugs ; 16(12)2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30563236

RESUMO

Marine macroalgae (seaweed) are an excellent source of novel bioactive metabolites. The biorefinery concept applied to seaweed facilitates the extraction of many chemical constituents from the same biomass ensuring that the resource is used fully, generating few residues through a succession of extraction steps. In the present study, the biomass of the carragenophyte Solieria filiformis (Rhodophyta, Gigartinales) cultured in an integrated multi-trophic aquaculture (IMTA) system was evaluated to obtain valuable products by a biorefinery approach. Enzymatic-assisted extraction (EAE) and microwave-assisted extraction (MAE) were the eco-friendly technologies used to ensure an environmentally friendly valorization of the biomass. Three valuable products were successfully recovered: a water-soluble extract rich in proteins and sulfated polysaccharides suitable as a food supplement; a lipid fraction rich in polyunsaturated fatty acids (PUFAs) with potential to be used in the nutraceutical industry; and a pure ι-carrageenan with a powerful antiviral activity against Herpes simplex virus (EC50 = 6.3 µg mL-1) comparable to the commercial antiviral acyclovir (EC50 = 3.2⁻5.4 µg mL-1).


Assuntos
Aquicultura/métodos , Produtos Biológicos/isolamento & purificação , Reatores Biológicos , Extratos Vegetais/isolamento & purificação , Rodófitas/química , Alga Marinha/química , Aciclovir/farmacologia , Animais , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Biomassa , Carragenina/química , Carragenina/isolamento & purificação , Carragenina/farmacologia , Suplementos Nutricionais , Enzimas/química , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/isolamento & purificação , Micro-Ondas , Perciformes/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Rodófitas/metabolismo , Pepinos-do-Mar/metabolismo , Alga Marinha/metabolismo , Simplexvirus/efeitos dos fármacos , Água/química
11.
Pharmazie ; 73(12): 733-736, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30522559

RESUMO

Propolis is a generic name for a biological substance produced by bees used for multiple purposes in folk medicine. Propolis special extract GH 2002 is crude propolis highly purified by a special procedure and freed from the accompanying substances like pollen, wax, resins. The cytotoxic and antiherpetic effect of propolis extracts against Varicella zoster virus (VZV) was analysed in cell culture, and revealed a moderate cytotoxicity on lung fibroblasts with a CC50 of 380 µg/ml. The 50 % inhibitory concentration (IC50) of GH 2002 propolis extract for VZV plaque formation was determined at 64 µg/ml. The propolis extract exhibited high levels of antiviral activity against VZV in viral suspension tests, infectivity was significantly reduced by 93.9 % and a direct concentration-dependent antiviral activity could be demonstrated. In order to determine the mode of virus suppression by propolis, the extract was added at different times during the viral infection cycle. Addition of propolis to uninfected cells (pretreatment cells) prior to infection or to infected cells (replication) during intracellular replication had no or only minor effect on virus multiplication. However, propolis exhibited high anti-VZV activity when viruses were pretreated with propolis prior to infection thus indicating an unspecific interaction between the virus and propolis. The antiviral activity is comparable to acyclovir.


Assuntos
Antivirais/farmacologia , Herpesvirus Humano 3/efeitos dos fármacos , Própole/farmacologia , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológico , Aciclovir/farmacologia , Animais , Antivirais/administração & dosagem , Abelhas , Linhagem Celular , Humanos , Concentração Inibidora 50 , Medicina Tradicional , Própole/administração & dosagem , Infecção pelo Vírus da Varicela-Zoster/virologia , Replicação Viral/efeitos dos fármacos
12.
Life Sci ; 215: 80-85, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30403989

RESUMO

AIMS AND METHODS: Many antiviral agents have been reported to present direct cytotoxic activity in cancer, showing antiproliferative and proapoptotic effects through different mechanisms. In the present study, we took into account the cytotoxic action of the antiviral drug acyclovir (ACV) on leukemia cells, by investigating cell cycle perturbations and apoptosis induction upon drug administration to three still unexplored cell lines, namely Jurkat, U937, and K562. At the same time, the cytotoxicity of cisplatin (CDDP) and 5­fluorouracil (5­FU) in combination with ACV was assessed, thus to evaluate if the antiviral agent could enhance cancer cell sensitivity to these chemotherapeutic drugs. FINDINGS AND SIGNIFICANCE: Our results showed that ACV cytotoxic action was maximum in Jurkat cells (acute T cell leukemia), which showed a dose- and time-dependent reduction of cell viability after drug exposure. The flow cytometric analysis of cell cycle revealed a delay/block in S phase and an increase of the sub-G1 peak upon ACV administration, thereby indicating apoptotic cell death. The activation of caspase-3 and the presence of nuclear DNA fragmentation confirmed the induction of apoptosis in ACV-treated cells. Interestingly, the pre-treatment of Jurkat cells with ACV for 72 h or 7 days increased CDDP and 5-FU cytotoxicity, suggesting enhanced leukemia cell sensitivity to these anticancer drugs.


Assuntos
Aciclovir/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cisplatino/farmacologia , Fluoruracila/farmacologia , Leucemia/tratamento farmacológico , Aciclovir/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Antivirais/administração & dosagem , Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/administração & dosagem , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Citometria de Fluxo , Fluoruracila/administração & dosagem , Humanos , Células Jurkat , Células K562 , Leucemia/patologia , Fatores de Tempo , Células U937
14.
J Fish Dis ; 41(11): 1709-1718, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30144085

RESUMO

Cyprinid herpesvirus 3 (CyHV-3), also known as koi herpesvirus (KHV), is an aetiological agent of a virulent and lethal disease in common and koi carp. In this study, we examined in vitro the anti-CyHV-3 activity of acyclovir (ACV), nucleoside analogue commonly used against human herpesviruses, as well as acyclovir monophospate (ACV-MP). The cytotoxicity of the ACV and the ACV-MP for two common carp cell lines, CCB (Common carp brain) and KF1 (Koi carp fin 1), was determined by means of MTT and crystal violet assays. In subsequent studies, the concentration of 66.67 µM was applied. The ACV and the ACV-MP (66.67 µM) inhibited a cytopathic effect (CPE) induced by the CyHV-3 virus in the CCB (ACV by 66%, ACV-MP by 58%) and the KF1 (ACV by 25%, ACV-MP by 37%). The viral load measured by the means of TaqMan qPCR was reduced in a range of 67%-93% depending on the analogue, the cell line and the time of incubation. The expression of viral genes (ORF149, ORF3, ORF134 and ORF78) in CCB cells infected with the CyHV-3 was strongly downregulated within the range of 78%-91%. In summary, both the ACV and the ACV-MP can inhibit CyHV-3 replication in vitro.


Assuntos
Aciclovir/farmacologia , Antivirais/farmacologia , Carpas/virologia , Herpesviridae/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Animais , Linhagem Celular
15.
J Virol Methods ; 260: 14-20, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29966597

RESUMO

Titration of the cell-associated virus (CAV) of varicella-zoster virus (VZV) is essential for antiviral studies. A VZV reporter cell line, MV9G, generated in our previous study expresses firefly luciferase upon CAV infection in a dose-dependent manner, suggesting that use of the cell line for titration is feasible. In this study, MeWo cells infected with VZV vaccine Oka (vOka) strain or with clinical isolates obtained from patients with varicella or zoster were used as CAV. A co-culture of MV9G cells with the virus-infected MeWo cells were set up and optimized for titration of CAV. Luciferase activities of MV9G cells measured as relative light units (RLUs) of chemiluminescence correlated well (r > 0.9, p < 0.05) both with quantities of viral DNAs measured by TaqMan PCR and with numbers of viral foci detected by immunostaining with a monoclonal antibody against VZV IE62. In addition, the usefulness of MV9G for antiviral studies was exemplified by treatment of the VZV-infected cells with various concentrations of acyclovir. Thus, the reporter cell-based titration of CAV by measuring the induced RLUs may be a reliable way to estimate viral foci and viral DNAs.


Assuntos
DNA Viral/isolamento & purificação , Genes Reporter/genética , Herpesvirus Humano 3/enzimologia , Infecção pelo Vírus da Varicela-Zoster/virologia , Carga Viral/genética , Aciclovir/farmacologia , Antivirais/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Técnicas de Cocultura , DNA Viral/efeitos dos fármacos , Herpesvirus Humano 3/efeitos dos fármacos , Humanos , Luciferases de Vaga-Lume/genética , Luminescência
16.
Cell Mol Biol (Noisy-le-grand) ; 64(8): 11-17, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29981678

RESUMO

The lack of an effective anti-viral agent and the emergence of drug-resistant strains dictate a real need for discovery of novel therapies able to ameliorate viral infections. In this regards, medicinal plants and natural products offer safe and inexpensive platforms for discovery of efficient and novel anti-viral agents. We have investigated the potential anti-viral activities of Veronica persica Poir.  as a medicinal plant against herpes simplex viruses (HSVs). In vitro screening of the ethanol plant extract against HSV-1 and HSV-2 infected Vero cells revealed the extract to show a dose-dependent inhibitory activity against both virus strains. After fractionation of the extract by a stepwise methanol gradient and evaluation of each fraction, the 80% methanol fraction displayed a pronounced inhibitory activity against the herpes viruses. The highest antiviral activity was observed when the Vero cells were treated with the extract both during and after infection by viruses. Moreover, the extract showed a prominent synergistic activity in combination with acyclovir anti-HSV therapy. Our findings revealed the potential of V. persica extract, especially its 80% methanol fraction, in inhibition of herpes simplex viral infections.


Assuntos
Antivirais/farmacologia , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Veronica/química , Aciclovir/farmacologia , Animais , Antivirais/química , Etanol/química , Herpes Zoster/virologia , Herpesvirus Humano 1/patogenicidade , Herpesvirus Humano 2/patogenicidade , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Células Vero/efeitos dos fármacos
17.
Jpn J Infect Dis ; 71(5): 343-349, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-29848849

RESUMO

Several cases of herpes simplex encephalitis (HSE) caused by acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) have been reported. Amino acid substitutions of R41H, Q125H, and A156V in the viral thymidine kinase (vTK) gene have been reported to confer ACV resistance. Recombinant HSV-1 clones, containing each amino acid substitution in the vTK gene, were generated using the bacterial artificial chromosome system. A recombinant HSV-1 with the Q125H substitution showed ACV resistance while the R41H or A156V substitutions were ACV-sensitive. Furthermore, the Q125H recombinant HSV-1 was less virulent than the repaired virus, but it maintained neurovirulence in mice at relatively high levels. Substitution of Q125H, which was detected in the neonatal HSE patient, conferred ACV resistance, but the substitutions of R41H and A156V, which were detected in immunocompetent adult HSE patients, did not. This suggests that HSE caused by ACV-resistant HSV-1 might be a very rare event to occur during the course of ACV treatment in immunocompetent patients. Showing resistance to ACV treatment does not always indicate emergence of ACV-resistant HSV-1 in HSE patients.


Assuntos
Aciclovir/farmacologia , Substituição de Aminoácidos , Antivirais/farmacologia , Encefalite por Herpes Simples/virologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/patogenicidade , Timidina Quinase/genética , Adulto , Idoso , Animais , Linhagem Celular , Cromossomos Artificiais Bacterianos , Modelos Animais de Doenças , Farmacorresistência Viral , Encefalite por Herpes Simples/patologia , Feminino , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/isolamento & purificação , Humanos , Recém-Nascido , Masculino , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Proteínas Mutantes/genética , Genética Reversa , Virulência , Fatores de Virulência/genética
19.
Anat Rec (Hoboken) ; 301(10): 1734-1744, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29729212

RESUMO

Herpes simplex virus type I (HSV-I) is a latent neuroinfection which can cause focal brain lesion. The role of HSV-infection in nerve regeneration has not been studied so far. The aim of the work was to study sciatic nerve regeneration in the presence of HSV-infection and the influence of an antiviral drug. BALB/c line mice were divided into five groups. Group 1 animals were infected with HSV-I. After resolution of neuroinfection manifestations the sciatic nerve of these animals was crushed. Group 2 mice were administered acyclovir following the same procedures. Groups 3-5 mice served as controls. Thirty days after the operation distal nerve stumps and m.gastrocnemius were studied morphologically and biochemically. Ultrastructural organization of the sciatic nerve in control animals remained intact. Morphometric parameters of the nerves from the experimental groups have not reach control values. However, in the group 1 diameter of nerve fibers was significantly smaller than in the group 2. Both nerve regeneration and m.gastrocnemius reinnervation were confirmed. The muscle hypotrophy was found in groups 1, 2, and 3 (the muscle fibers diameter decreased). Metabolic changes in the muscles of the infected animals (groups 1 and 2) were more pronounced than in control groups 3 and 4. The levels of TBA-active products, conjugated dienes, carbonyl and SH-groups were reduced in m.gastrocnemius of the experimental groups, however no significant difference associated with acyclovir administration was found. HSV-infection is not limited to the local neurodegenerative changes in the CNS but affects regeneration of the injured sciatic nerve. Anat Rec, 301:1734-1744, 2018. © 2018 Wiley Periodicals, Inc.


Assuntos
Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Herpes Simples/tratamento farmacológico , Regeneração Nervosa/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Aciclovir/farmacologia , Animais , Antivirais/farmacologia , Avaliação Pré-Clínica de Medicamentos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Nervo Isquiático/ultraestrutura
20.
Mater Sci Eng C Mater Biol Appl ; 89: 413-421, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29752114

RESUMO

This work relates to quasi spherical gold nanoparticles synthesis and successful antiviral efficacy evaluations against Herpes simplex virus (HSV) infections. Ultrasound induced rapid reduction in gallic acid (GA) leads to highly monodispersed gold nanoparticles (GAunps). GAunps plasmonic peak was recorded at 531 nm with TEM size of 7.86 nm. X-ray diffraction and SAED pattern proved fcc crystalline structure. FTIR studies confirmed nanoparticles surface conjugation with gallic acid. The antiviral efficacy of GAunps was studied against HSV infections in Vero cells. GAunps were effective in dose-dependent manner with EC50 of 32.3 µM in HSV-1 and 38.6 µM in HSV-2. Further study revealed that GAunps prevented viral attachment and penetration into the Vero cells. The inhibition percentage varied with the nanoparticles exposure time in infected cells. Nanoparticles cytotoxicity (CC50 972.4 µM) in Vero cells was significantly lower than acyclovir (CC50 561.7 µM) indicating its safety. Bio-safe gold nanoparticles were proposed as a safer alternative in virus chemotherapy.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Aciclovir/farmacologia , Animais , Antivirais/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Ácido Gálico/química , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 2/fisiologia , Nanopartículas Metálicas/toxicidade , Espectroscopia de Infravermelho com Transformada de Fourier , Células Vero , Internalização do Vírus/efeitos dos fármacos , Difração de Raios X
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