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1.
Viruses ; 13(2)2021 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672561

RESUMO

In the face of new emerging respiratory viruses, such as SARS-CoV2, vaccines and drug therapies are not immediately available to curb the spread of infection. Non-pharmaceutical interventions, such as mask-wearing and social distance, can slow the transmission. However, both mask and social distance have not prevented the spread of respiratory viruses SARS-CoV2 within the US. There is an urgent need to develop an intervention that could reduce the spread of respiratory viruses. The key to preventing transmission is to eliminate the emission of SARS-CoV2 from an infected person and stop the virus from propagating in the human population. Rhamnolipids are environmentally friendly surfactants that are less toxic than the synthetic surfactants. In this study, rhamnolipid products, 222B, were investigated as disinfectants against enveloped viruses, such as bovine coronavirus and herpes simplex virus 1 (HSV-1). The 222B at 0.009% and 0.0045% completely inactivated 6 and 4 log PFU/mL of HSV-1 in 5-10 min, respectively. 222B at or below 0.005% is also biologically safe. Moreover, 50 µL of 222B at 0.005% on ~1 cm2 mask fabrics or plastic surface can inactivate ~103 PFU HSV-1 in 3-5 min. These results suggest that 222B coated on masks or plastic surface can reduce the emission of SARS-CoV2 from an infected person and stop the spread of SARS-CoV2.


Assuntos
COVID-19 , Coronavirus Bovino/efeitos dos fármacos , Desinfetantes/farmacologia , Glicolipídeos/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Tensoativos/farmacologia , COVID-19/prevenção & controle , COVID-19/transmissão , Humanos
2.
Viruses ; 13(2)2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525505

RESUMO

The herpes simplex virus 1 (HSV-1) genome is extremely rich in guanine tracts that fold into G-quadruplexes (G4s), nucleic acid secondary structures implicated in key biological functions. Viral G4s were visualized in HSV-1 infected cells, with massive virus cycle-dependent G4-formation peaking during viral DNA replication. Small molecules that specifically interact with G4s have been shown to inhibit HSV-1 DNA replication. We here investigated the antiviral activity of TMPyP4, a porphyrin known to interact with G4s. The analogue TMPyP2, with lower G4 affinity, was used as control. We showed by biophysical analysis that TMPyP4 interacts with HSV-1 G4s, and inhibits polymerase progression in vitro; in infected cells, it displayed good antiviral activity which, however, was independent of inhibition of virus DNA replication or entry. At low TMPyP4 concentration, the virus released by the cells was almost null, while inside the cell virus amounts were at control levels. TEM analysis showed that virus particles were trapped inside cytoplasmatic vesicles, which could not be ascribed to autophagy, as proven by RT-qPCR, western blot, and immunofluorescence analysis. Our data indicate a unique mechanism of action of TMPyP4 against HSV-1, and suggest the unprecedented involvement of currently unknown G4s in viral or antiviral cellular defense pathways.


Assuntos
Antivirais/farmacologia , Quadruplex G/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Porfirinas/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/química , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Vesículas Citoplasmáticas/efeitos dos fármacos , Vesículas Citoplasmáticas/metabolismo , DNA Viral/química , DNA Viral/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Ligantes , Estrutura Molecular , Porfirinas/química , Células Vero , Vírion/efeitos dos fármacos , Vírion/metabolismo
3.
Viruses ; 13(1)2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33435520

RESUMO

Herpes simplex virus type 1 (HSV-1) causes a lifelong latent infection with an estimated global prevalence of 66%. Primary and recurrent HSV infections are characterized by a tingling sensation, followed by an eruption of vesicles, which can cause painful erosions. Commonly used antiviral drugs against HSV infection are nucleoside analogues including acyclovir (ACV), famciclovir, and valacyclovir. Although these nucleoside analogues reduce morbidity and mortality in immunocompetent individuals, ACV-resistant HSV strains (ACVR-HSV) have been isolated from immunocompromised patients. Thus, ACVR-HSV infection poses a critical emerging public health concern. Recently, we reported that ginkgolic acid (GA) inhibits HSV-1 by disrupting viral structure, blocking fusion, and inhibiting viral protein synthesis. Additionally, we showed GA affords a broad spectrum of fusion inhibition of all three classes of fusion proteins, including those of HIV, Ebola, influenza A and Epstein Barr viruses. Here we report GA's antiviral activity against HSV-1 skin infection in BALB/cJ mice. GA-treated mice demonstrated a significantly reduced mortality rate and decreased infection scores compared to controls treated with dimethylsulfoxide (DMSO)-vehicle. Furthermore, GA efficiently inhibited ACVR-HSV-1 strain 17+ in vitro and in vivo. Since GA's mechanism of action includes virucidal activity and fusion inhibition, it is expected to work alone or synergistically with other anti-viral drugs, and we anticipate it to be effective against additional cutaneous and potentially systemic viral infections.


Assuntos
Antivirais/farmacologia , Dermatite/virologia , Herpes Simples/virologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Salicilatos/farmacologia , Animais , Linhagem Celular , Chlorocebus aethiops , Dermatite/tratamento farmacológico , Modelos Animais de Doenças , Herpes Simples/tratamento farmacológico , Herpes Simples/transmissão , Camundongos , Células Vero , Ensaio de Placa Viral , Replicação Viral/efeitos dos fármacos
4.
Int J Biol Macromol ; 168: 322-330, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33310095

RESUMO

Solieria filiformis has been reported to have molecules with various biological activities. In this study we used environmentally friendly extraction methods, such as enzyme-assisted extraction (EAE), as a first step to obtain bioactive compounds from this species. Five combinations of protease (PRO) and carbohydrase (AMG) were utilized (1:0, 0:1, 2:1, 1:1, 1:2 PRO:AMG) to obtain Water Soluble Enzymatic Hydrolysates (WSEHs). Extraction yields, biochemical and structural characterization, as well as in vitro activity against Herpes simplex virus type 1 (HSV-1) and antioxidant capacities were determined. All PRO:AMG combinations significantly improved yields. EAE yielded heterogeneous extracts rich in iota-carrageenan and phenols, as confirmed by FTIR spectra. The highest antiherpetic activity (EC50 4.5 ± 0.4 µg mL-1) was found in the WSEHs obtained under 2:1 PRO:AMG. At this combination high antioxidant capacity was also obtained for ABTS (2,2'-Azino-Bis-3-ethylbenzoThiazoline-6-Sulfonic acid) radical scavenging activity and Ferric Reducing Antioxidant Power (FRAP). These could probably play a synergistic role associated to the strong antiviral activity obtained. These results suggest that 2:1 PRO:AMG could be effective in promoting the hydrolytic breakdown of high MW polysaccharides, contributing to the improvement of WSEHs bioactivity. Although Solieria filiformis WSEHs showed promising results, further research, including separation and purification techniques are needed.


Assuntos
Carragenina/química , Carragenina/farmacologia , Rodófitas/enzimologia , Antioxidantes/química , Antivirais/química , Compostos de Bifenilo/química , Herpesvirus Humano 1/efeitos dos fármacos , Fenóis/química , Picratos/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Rodófitas/química
6.
Viruses ; 12(12)2020 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-33322225

RESUMO

Acyclovir is the drug of choice for the treatment of herpes simplex virus (HSV) infections. Acyclovir-resistant HSV strains may emerge, especially during long-term drug use, and subsequently cause difficult-to-treat exacerbations. Previously, we set up a novel treatment approach, based on enzymatically synthesized pools of siRNAs, or siRNA swarms. These swarms can cover kilobases-long target sequences, reducing the likelihood of resistance to treatment. Swarms targeting the UL29 essential gene of HSV-1 have demonstrated high efficacy against HSV-1 in vitro and in vivo. Here, we assessed the antiviral potential of a UL29 siRNA swarm against circulating strains of HSV-1, in comparison with acyclovir. All circulating strains were sensitive to both antivirals, with the half-maximal inhibitory concentrations (IC50) in the range of 350-1911 nM for acyclovir and 0.5-3 nM for the UL29 siRNA swarm. Additionally, we showed that an acyclovir-resistant HSV-1, devoid of thymidine kinase, is highly sensitive to UL29 siRNA treatment (IC50 1.0 nM; Imax 97%). Moreover, the detected minor variations in the RNAi target of the HSV strains had no effect on the potency or efficacy of UL29 siRNA swarm treatment. Our findings support the development of siRNA swarms for the treatment of HSV-1 infections, in order to circumvent any potential acyclovir resistance.


Assuntos
Aciclovir/farmacologia , Proteínas de Ligação a DNA/genética , Herpes Simples/virologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Proteínas Virais/genética , Aciclovir/uso terapêutico , Animais , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Farmacorresistência Viral/efeitos dos fármacos , Farmacorresistência Viral/genética , Herpes Simples/terapia , Herpesvirus Humano 1/classificação , Herpesvirus Humano 1/isolamento & purificação , Humanos , Concentração Inibidora 50 , Células Vero
7.
BMC Infect Dis ; 20(1): 832, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176697

RESUMO

BACKGROUND: Carvacrol, as the major components of aromatic plants used for treating human skin diseases including origanum, Satureja, thymus, and coridothymus species, presented a kind of antiviral activity. To explore the mechanisms of carvacrol against herpes simplex virus (HSV) in vitro. METHOD: The BSC-1 cells model of HSV infection was established, and from the two aspects of viral replication level and cell death pathway, the antiviral effects of carvacrol on HSV infected cells were also evaluated by plaque assay under the three modes including prevention, treatment, and direct inactivation. RESULTS: In the three ways, the half-maximal effective concentration (EC50) of 2% true carvacrol solution on HSV-2 infected cells were severally 0.43, 0.19 and 0.51 mmol/L, and the corresponding therapeutic index (TI) were 4.02, 9.11 and 3.39, respectively. It's the opposite of the increased levels caused by HSV-2 infection, that both the expressions at the transcription genes and protein levels of virus own replication key factors (including ICP4, ICP27, VP16, gB, and UL30) and cytokines (including RIP3, TNF-α, and MLKL) of infected cells treated with carvacrol were dose-dependently inhibited. Besides, HSV-2 infection can cause the decrease of intracellular protein ubiquitination level, and carvacrol can reverse the ubiquitination decrease level caused by HSV-2 infection. CONCLUSION: Carvacrol exhibits significant antiviral activity by inhibiting the HSV-2 proliferation process and HSV-2-induced TNF-α increasing levels, decreasing RIP3 and MLKL protein expressions through the intracellular RIP3-mediated programmed cell necrosis pathway. In addition, carvacrol also may exhibit anti-HSV-2 activity by reversing the ubiquitination decrease level caused by HSV-2 infection on the ubiquitin-proteasome system, which provides insights into the molecular mechanism.


Assuntos
Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Cimenos/farmacologia , Células Epiteliais/virologia , Herpes Simples/metabolismo , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Ubiquitina/metabolismo , Animais , Chlorocebus aethiops , Citocinas/metabolismo , Herpes Simples/virologia , Transdução de Sinais/efeitos dos fármacos , Células Vero , Replicação Viral/efeitos dos fármacos
8.
Sci Rep ; 10(1): 8599, 2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32451388

RESUMO

The antiviral activity of schizonepetin derivatives 1A-1C were investigated via theoretical methods and results are compared with experimental results. The derivatives 1 A and 1 C have the highest and the lowest antiviral activity, respectively. The interactions of derivatives 1A-1C and BN-nanotube are examined. Results show that, derivatives 1A-1C can effectively interact with BN-nanotube (9, 9) and their adsorptions are favorable. The energy of derivative 1 A is higher than derivatives 1B and 1 C. The derivative 1 A has highest absolute µ, ω and ∆N values and it has lowest absolute ƞ value. Results show that, theoretical and experimental trends of antiviral activity of derivatives 1A-1C were similar, successfully.


Assuntos
Antivirais/síntese química , Monoterpenos/química , Adsorção , Antivirais/química , Antivirais/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Monoterpenos/síntese química , Monoterpenos/farmacologia , Nanotubos/química , Teoria Quântica
9.
Nat Commun ; 11(1): 2038, 2020 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341360

RESUMO

The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of ORFs as well as N-terminal extensions (NTEs) and truncations. We show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins. We extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution.


Assuntos
Genoma Viral , Herpesvirus Humano 1/genética , Animais , Produtos Biológicos/farmacologia , Chlorocebus aethiops , Biologia Computacional , Cricetinae , Fibroblastos/metabolismo , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Genes Virais , Genômica , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Fases de Leitura Aberta , Domínios Proteicos , Isoformas de Proteínas , Ribossomos/metabolismo , Transcriptoma , Células Vero
10.
Sci Rep ; 10(1): 6671, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32317666

RESUMO

Herpes simplex virus 1 (HSV-1) causes a number of clinical manifestations including cold sores, keratitis, meningitis and encephalitis. Although current drugs are available to treat HSV-1 infection, they can cause side effects such as nephrotoxicity. Moreover, owing to the emergence of drug-resistant HSV-1 strains, new anti-HSV-1 compounds are needed. Because many viruses exploit cellular host proteases and encode their own viral proteases for survival, we investigated the inhibitory effects of a panel of protease inhibitors (TLCK, TPCK, E64, bortezomib, or MG132) on HSV-1 replication and several host cell signaling pathways. We found that HSV-1 infection suppressed c-Raf-MEK1/2-ERK1/2-p90RSK signaling in host cells, which facilitated viral replication. The mechanism by which HSV-1 inhibited ERK signaling was mediated through the polyubiquitination and proteasomal degradation of Ras-guanine nucleotide-releasing factor 2 (Ras-GRF2). Importantly, the proteasome inhibitor MG132 inhibited HSV-1 replication by reversing ERK suppression in infected cells, inhibiting lytic genes (ICP5, ICP27 and UL42) expression, and overcoming the downregulation of Ras-GRF2. These results indicate that the suppression of ERK signaling via proteasomal degradation of Ras-GRF2 is necessary for HSV-1 infection and replication. Given that ERK activation by MG132 exhibits anti-HSV-1 activity, these results suggest that the proteasome inhibitor could serve as a novel therapeutic agent against HSV-1 infection.


Assuntos
Antivirais/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Leupeptinas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Bortezomib/farmacologia , Caspases/metabolismo , Chlorocebus aethiops , Replicação do DNA/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Leucina/análogos & derivados , Leucina/farmacologia , Modelos Biológicos , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Poliubiquitina/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Estabilidade Proteica/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Tosilina Clorometil Cetona/farmacologia , Tosilfenilalanil Clorometil Cetona/farmacologia , Células Vero , Replicação Viral/efeitos dos fármacos
11.
Arch Virol ; 165(6): 1385-1396, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32346764

RESUMO

Human herpesviruses are among the most prevalent pathogens worldwide and have become an important public health issue. Recurrent infections and the emergence of resistant viral strains reinforce the need of searching new drugs to treat herpes virus infections. Cardiac glycosides are used clinically to treat cardiovascular disturbances, such as congestive heart failure and atrial arrhythmias. In recent years, they have sparked new interest in their potential anti-herpes action. It has been previously reported by our research group that two new semisynthetic cardenolides, namely C10 (3ß-[(N-(2-hydroxyethyl)aminoacetyl]amino-3-deoxydigitoxigenin) and C11 (3ß-(hydroxyacetyl)amino-3-deoxydigitoxigenin), exhibited potential anti-HSV-1 and anti-HSV-2 with selectivity index values > 1,000, comparable with those of acyclovir. This work reports the mechanism investigation of anti-herpes action of these derivatives. The results demonstrated that C10 and C11 interfere with the intermediate and final steps of HSV replication, but not with the early stages, since they completely abolished the expression of the UL42 (ß) and gD (γ) proteins and partially reduced that of ICP27 (α). Additionally, they were not virucidal and had no prophylactic effects. Both compounds inhibited HSV replication at nanomolar concentrations, but cardenolide C10 was more active than C11 and can be considered as an anti-herpes drug candidate including against acyclovir-resistant HSV-1 strains.


Assuntos
Antivirais/farmacologia , Cardenolídeos/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Aciclovir/farmacologia , Animais , Antivirais/síntese química , Cardenolídeos/síntese química , Chlorocebus aethiops , Avaliação Pré-Clínica de Medicamentos , Farmacorresistência Viral , Infecções por Herpesviridae/tratamento farmacológico , Humanos , Células Vero
12.
Sci Adv ; 6(5): eaax9318, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32064341

RESUMO

Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal. Unfortunately, all virucidal molecules described to date are cytotoxic. We recently developed nontoxic, broad-spectrum virucidal gold nanoparticles. Here, we develop further the concept and describe cyclodextrins, modified with mercaptoundecane sulfonic acids, to mimic heparan sulfates and to provide the key nontoxic virucidal action. We show that the resulting macromolecules are broad-spectrum, biocompatible, and virucidal at micromolar concentrations in vitro against many viruses [including herpes simplex virus (HSV), respiratory syncytial virus (RSV), dengue virus, and Zika virus]. They are effective ex vivo against both laboratory and clinical strains of RSV and HSV-2 in respiratory and vaginal tissue culture models, respectively. Additionally, they are effective when administrated in mice before intravaginal HSV-2 inoculation. Lastly, they pass a mutation resistance test that the currently available anti-HSV drug (acyclovir) fails.


Assuntos
Ciclodextrinas/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Viroses/tratamento farmacológico , Aciclovir/química , Aciclovir/farmacologia , Animais , Antivirais/síntese química , Antivirais/química , Antivirais/farmacologia , Ciclodextrinas/síntese química , Ciclodextrinas/química , Feminino , Ouro/química , Heparitina Sulfato/química , Heparitina Sulfato/farmacologia , Herpesvirus Humano 1/patogenicidade , Herpesvirus Humano 2/patogenicidade , Humanos , Nanopartículas Metálicas/química , Camundongos , Simplexvirus/efeitos dos fármacos , Simplexvirus/patogenicidade , Viroses/virologia , Zika virus/efeitos dos fármacos , Zika virus/patogenicidade
13.
Mikrobiyol Bul ; 54(1): 79-94, 2020 Jan.
Artigo em Turco | MEDLINE | ID: mdl-32050880

RESUMO

While acyclovir, a nucleoside analogue, is widely used for herpes simplex virus type 1 (HSV-1), emergence of drug-resistant viruses due to frequent usage of this class of medicines, and their toxic side effects require exploring novel active molecules. Despite the studies on developing synthetic molecules in medical sciences and pharmacology, herbs as a natural source of biologically-active compounds remain popular. In this in vitro study, olive leaf extract (OLE) and propolis alone or in combination with acyclovir were investigated for their antiviral efficacy in HSV-1.Toxic doses of OLE, propolis, and dimethyl sulfoxide, propolis diluent, for Hep-2 (ATCC, CCL-23) cells were determined by conventional cell culture. Using "endpoint" method, the viral dose infecting half of the cell culture (TCID50) was calculated, and viral quantity was determined with Spearman-Karber method. Antiviral effects of OLE and propolis on HSV-1 were investigated by conventional cell culture and real-time cell analysis (RTCA). Combinations of the two extracts with one another and with acyclovir were evaluated by RTCA. Active substances prepared at three different dilutions were added to tubes with HSV-1 of logTCID50: 11.5 in descending order starting from the highest non-toxic concentration, and they were left at room temperature for two different durations (one hour and three hours). The aliquots taken from the tubes were cultured in plates containing Hep-2 cells and evaluated after 72 hours. Combinations of extracts and acyclovir at concentrations at least four times lower than the lowest concentration showing antiviral efficacy against HSV-1 were cultured with Hep-2 cells in the e-plates of the xCELLigence RTCA device, measurements were obtained at 30 minute intervals, and data were recorded in real time. In the test with two different durations and at different concentrations of OLE and propolis, antiviral efficacy was observed both with one-hour and three-hour incubation at a concentration of 10 µg/ ml for propolis and 1.2 mg/ml for OLE with RTCA. The duration and concentration of the greatest decrease in viral quantity were in the first one hour and 10 µg/ml for propolis, and in the first one hour and 1.2 mg/ ml for OLE. Combination of propolis and OLE with acyclovir caused no cytopathic effects, and the combination of extracts led to delayed cytopathic effect. According to these results, propolis and OLE, alone and in combinations with acyclovir, have antiviral efficacy against HSV-1. These agents may reduce the dose and side effects of acyclovir in case of co-administration since they exert their effects through a different mechanism than acyclovir,possibly through direct virucidal activity, inhibition of virus internalization or viral inhibition in early stages of replication (inhibition of adsorption/binding of viral particles to the cell). These extracts that do not require conversion to active form have the potential to reduce infectivity in oral lesions, prevent spread, and be used in the topical treatment of acyclovir-resistant HSV infections, particularly in immunocompromised patients. However, in vivo studies should be conducted to determine their medicinal properties and potential toxicities. These results should be supported by further comprehensive studies and the efficacy against other viruses should also be investigated.


Assuntos
Aciclovir , Antivirais , Herpesvirus Humano 1 , Olea , Extratos Vegetais , Própole , Aciclovir/farmacologia , Antivirais/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Olea/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Própole/farmacologia
15.
J Gen Virol ; 101(2): 208-215, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31961788

RESUMO

In previous studies, cold atmospheric plasma (CAP) was explored as an antibacterial and antiviral agent for the treatment of chronic wounds. The aim of the present study was to investigate whether CAP may also be suitable as an antiviral therapy against herpes simplex virus type 1 (HSV-1). HSV-1 most frequently manifests as recurrent herpes labialis, but it can also cause encephalitis, conjunctivitis or herpes neonatorum as a perinatal infection. HSV-1 encoding the reporter gene GFP was propagated. The CAP dose for HSV-1 treatment was gradually increased, ranging from 0-150 s, and aciclovir was used as a positive control. After CAP treatment, the virus suspension was applied to a standard HSV research cell line (Vero cells) and the neuroblastoma cell line SH-SY5Y as a model for neuronal infection. The results showed that plasma treatment had a negligible antiviral effect on HSV-1 in both Vero- and SH-SY5Y cells at high dose. However, when we lowered the viral load 100-fold, we observed a significantly decreased number of internalized HSV-1 genomes 3 h post-infection for CAP-treated viruses. This difference was less pronounced with respect to GFP expression levels 24 h post-infection, which was in sharp contrast to the acyclovir-treated positive control, for which the viral load was reduced from 95 to 25%. In summary, we observed a low but measurable antiviral effect of CAP on HSV-1.


Assuntos
Herpes Simples/terapia , Herpesvirus Humano 1/efeitos dos fármacos , Gases em Plasma/farmacologia , Aciclovir/farmacologia , Animais , Antivirais/farmacologia , Linhagem Celular , Chlorocebus aethiops , Humanos , Células Vero
16.
Phytochemistry ; 171: 112229, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901474

RESUMO

Seven undescribed cycloartane triterpenoids, pseudolarnoids A-G, together with ten known ones, were isolated from the seeds of Pseudolarix amabilis (J. Nelson) Rehder. Their structures were elucidated on the basis of spectroscopic analysis, X-ray crystallography, and ECD data. Pseudolarnoids A-C are cycloartane triterpenoids with a unique 16S, 23R-spirolactone moiety. Pseudolarnoids F, G, and pseudolarolide C demonstrated potent antiviral effects on HSV-1 in vitro.


Assuntos
Antivirais/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Triterpenos/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Cristalografia por Raios X , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Pinaceae/química , Triterpenos/química , Triterpenos/isolamento & purificação
17.
Microb Pathog ; 140: 103961, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31904451

RESUMO

OBJECTIVE: To investigate the effect of lipopolysaccharide (LPS) on human herpesvirus 1 (HHV-1) infection in epithelial cells. METHODS: Two strains of HHV-1, HHV-1 F strain (HHV-1f) and HHV-1 strain-H129 with GFP knock-in (HHV-g4), were used to infect HCE-T and VERO cells at MOIs of 0.04 and 0.02, respectively. After 1 h, 0, 10, 50, and 100 µg/ml LPS was added to serum-free medium and the cells were cultured for up to 24 h. GFP fluorescence of HHV-g4 in cells was examined under a fluorescence microscope and imaged. HHV-1f titer was determined by quantitative real-time polymerase chain reaction (qPCR) in HCE-T cells and plaque assays in VERO cells. The expression of the viral ICP4 protein of HHV-1f was detected by Western blot assay. IL-6 and IL-10 levels in culture medium were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Similar changes but at different degrees were found in HCE-T and VERO cells that were infected with HHV-1. GFP fluorescence of HHV-g4 and cell lesions increased in a dose-dependent manner. Virus titer was also enhanced by LPS stimulation in HCE-T and VERO cells. ICP4 expression was promoted at higher LPS concentrations (P = 0.04). In addition, viral infection resulted in increased expression of IL-6 in a dose-dependent manner at 12 and 24 h (P = 0.01), while IL-10 expression was unaffected by either HHV-1 infection or LPS stimulation. CONCLUSION: LPS promotes HHV-1 infection in epithelial cells, which suggests that gram-negative bacteria on ocular surfaces may aggravate HHV-1 infection.


Assuntos
Células Epiteliais/metabolismo , Herpes Simples/metabolismo , Herpesvirus Humano 1/fisiologia , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Animais , Chlorocebus aethiops , Células Epiteliais/virologia , Herpes Simples/genética , Herpes Simples/virologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/genética , Humanos , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Interleucina-6/genética , Células Vero , Replicação Viral
18.
Chem Biodivers ; 17(2): e1900511, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31800173

RESUMO

The in vitro cytotoxic activity in Vero cells and the antiviral activity of Erythrina speciosa methanol extract, fractions, and isolated vitexin were studied. The results revealed that E. speciosa leaves ethyl acetate soluble fraction of the methanol extract (ESLE) was the most active against herpes simplex virus type 1 (HSV-1). Bioactivity-guided fractionation was performed on ESLE to isolate the bioactive compounds responsible for this activity. One sub-fraction from ESLE (ESLE IV) showed the highest activity against HSV-1 and Hepatitis A HAV-H10 viruses. Vitexin isolated from ESLE VI exhibited a significant antiviral activity (EC50 =35±2.7 and 18±3.3 µg/mL against HAV-H10 and HSV-1 virus, respectively), which was notably greater than the activity of the extract and the fractions. Molecular docking studies were carried out to explore the molecular interactions of vitexin with different macromolecular targets. Analysis of the in silico data together with the in vitro studies validated the antiviral activity associated with vitexin. These outcomes indicated that vitexin is a potential candidate to be utilized commendably in lead optimization for the development of antiviral agents.


Assuntos
Antivirais/metabolismo , Apigenina/metabolismo , Erythrina/química , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Antivirais/química , Antivirais/farmacologia , Apigenina/química , Apigenina/farmacologia , Sítios de Ligação , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , DNA Polimerase Dirigida por DNA/química , DNA Polimerase Dirigida por DNA/metabolismo , Erythrina/metabolismo , Frutas/química , Frutas/metabolismo , Vírus da Hepatite A/efeitos dos fármacos , Vírus da Hepatite A/metabolismo , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/metabolismo , Proteínas Virais/química , Proteínas Virais/metabolismo
19.
Cornea ; 39(2): 196-199, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31738241

RESUMO

PURPOSE: To report the outcomes of Descemet membrane endothelial keratoplasty (DMEK) with intensive antiviral therapy for corneal edema secondary to herpes simplex virus type 1 (HSV-1)-mediated endotheliitis. METHODS: All eyes with polymerase chain reaction positive for HSV-1 undergoing DMEK for endothelial decompensation between January 2014 and January 2018 were followed up prospectively at our tertiary referral center. All eyes had been free of active inflammation for a minimum of 9 months and were treated prophylactically with high-dose systemic and topical antivirals, which were continued for a prolonged period of time. Primary outcomes were the occurrence of immunological rejection and/or recurrence of endotheliitis, eventually resulting in graft failure. Secondary outcomes were best spectacle-corrected visual acuity and endothelial cell loss. RESULTS: Four consecutive eyes of 4 patients were included with a mean (±SD) patient age of 68.5 ± 15.1 years. The postoperative follow-up averaged 22 months. No eyes exhibited any signs of immunologic rejection, recurrence of endotheliitis, or graft failure. Mean (±SD) decimal best spectacle-corrected visual acuity improved from 0.2 ± 0.1 to 0.7 ± 0.2 (P = 0.007), whereas mean (±SD) endothelial cell loss was 56% ± 10.2% at the final postoperative follow-up. CONCLUSIONS: DMEK is an effective option to treat corneal edema secondary to HSV-1-related endotheliitis. Intensive antiviral prophylaxis may reduce the risk of recurrence and subsequent graft failure.


Assuntos
Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Epitélio Posterior/patologia , Ceratite Herpética/terapia , Administração Oftálmica , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Ganciclovir/uso terapêutico , Sobrevivência de Enxerto/fisiologia , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Ceratite Herpética/diagnóstico , Ceratite Herpética/tratamento farmacológico , Ceratite Herpética/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Microscopia com Lâmpada de Fenda , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia
20.
Carbohydr Polym ; 229: 115487, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826428

RESUMO

Purified fucoidans SHAP-1 and SHAP-2 with apparent molecular weights of 6.55 × 105 and 5.89 × 105, respectively, were isolated from Sargassum henslowianum by ion-exchange and gel-filtration column chromatography. They are both composed of fucose and galactose at a ratio of around 3:1 and 31.9% sulfate. The backbone of two fucoidans consists of α-(1→3)-linked L-Fucp residues which are mainly sulfated on the C-2 and C-4 positions. Side chains composed of terminally linked α-L-Fucp and α-D-Galp residues, and (1→2)-, (1→6)-, and (1→2,6)-linked ß-D-Galp residues attach mainly at O-4 position of backbone residues. Antiviral test showed that the IC50 values of SHAP-1 and SHAP-2 against HSV-1 were estimated to be 0.89 and 0.82 µg/mL by plaque reduction assay, respectively, whereas both as low as 0.48 µg/mL against HSV-2. The antiviral mechanism of the fucoidans might be at least through blocking HSV-2 virion adsorption to host cells. These results suggest that the fucoidans have potential clinical applications.


Assuntos
Antivirais/química , Antivirais/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Sargassum/química , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos
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