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1.
Microb Cell Fact ; 23(1): 117, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38644470

RESUMO

Several antiviral agents lost their efficacy due to their severe side effects and virus mutations. This study aimed to identify and optimize the conditions for exopolysaccharide (EPS) production from a newly isolated cyanobacterium, Acaryochloris Al-Azhar MNE ON864448.1, besides exploring its antiviral activity. The cyanobacterial EPS was purified through DEAE-52 cellulose column with a final yield of 83.75%. Different analysis instruments were applied for EPS identification, including Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), and gas chromatographic-mass spectrometry (GC-MS). Plackett-Burman's design demonstrated that working volume (X1), EDTA (X2), inoculum size (X3), CaCl2 (X4), and NaCl (X5) are the most important variables influencing EPS production. Central composite design (CCD) exhibited maximum EPS yield (9.27 mg/mL) at a working volume of 300 mL in a 1 L volumetric flask, EDTA 0.002 g/L, inoculum size 7%, CaCl2 0.046 g/L, and NaCl 20 g/L were applied. EPS showed potent antiviral activities at different stages of herpes simplex virus type-1 and 2 (HSV-1, HSV-2), adenovirus (ADV) and coxsackievirus (A16) infections. The highest half-maximal inhibitory concentration (IC50) (6.477 µg/mL) was recorded during HSV-1 internalization mechanism, while the lowest IC50 (0.005669 µg/mL) was recorded during coxsackievirus neutralization mechanism.


Assuntos
Antivirais , Cianobactérias , Polissacarídeos Bacterianos , Antivirais/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Cianobactérias/química , Polissacarídeos Bacterianos/farmacologia , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/isolamento & purificação , Polissacarídeos Bacterianos/biossíntese , Animais , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier , Chlorocebus aethiops
2.
Phytomedicine ; 110: 154650, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36649670

RESUMO

BACKGROUND: Dengue caused by dengue virus (DENV) spreads rapidly around the world. However, there are no worldwide licensed vaccines or specific antivirals to combat DENV infection. Quassinoids are the most characteristic components of Eurycoma longifolia, which have been reported to display a variety of biological activities. However, whether quassinoids exert anti-DENV activities remains unknown. PURPOSE: To test the quassinoids of E. longifolia for their activity against DENV and to clarify the potential mechanisms. METHODS: The quassinoids from E. longifolia were isolated by chromatography techniques, and their chemical structures were elucidated by spectroscopic analysis. The anti-DENV activities of quassinoids on baby hamster kidney cells BHK-21 were determined by lactate dehydrogenase (LDH) assay. The synthesis of progeny virus was measured by plaque assay. The expression levels of envelope protein (E) and non-structural protein 1 (NS1) were evaluated by qRT-PCR, Western blot and immunofluorescence assays. Molecular docking was used to screen the potential targets of the most active quassinoid against DENV-2, and surface plasmon resonance analysis was employed to confirm the direct binding between the most active quassinoid and potential target. RESULTS: Twenty-four quassinoids, including three new quassinoids (1 - 3), were isolated from the ethanol extract of E. longifolia. Quassinoids 4, 5, 9, 11, 12, 15, 16, 17, 19 and 20 significantly reduced the LDH release at the stages of viral binding and entry or intracellular replication. Among them, 19 (6α-hydroxyeurycomalactone, 6α-HEL) exhibited the best anti-DENV-2 activities with an EC50 value of 0.39 ± 0.02 µM. Further experiments suggested that 6α-HEL remarkably inhibited progeny virus synthesis and mRNA and protein expression levels of E and NS1 of DENV-2. Time-of-drug-addition assay suggested that 6α-HEL inhibited intracellular replication of DENV-2 at an early stage. Moreover, 6α-HEL was shown to interact with NS5-RdRp domain at a binding affinity of -8.15 kcal/mol. SPR assay further verified 6α-HEL bound to RdRp protein with an equilibrium dissociation constant of 1.49 × 10-7 M. CONCLUSION: Ten quassinoids from E. longifolia showed anti-DENV activities at processes of virus binding and entry or intracellular replication. The most active quassinoid 6α-HEL exerts the anti-DENV-2 activities at intracellular replication stage by directly targeting the NS5-RdRp protein. These results suggest that 6α-HEL could be a promising candidate for the treatment of DENV-2 infection.


Assuntos
Antivirais , Vírus da Dengue , Eurycoma , Quassinas , Replicação Viral , Animais , Cricetinae , Humanos , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Dengue/tratamento farmacológico , Eurycoma/química , Simulação de Acoplamento Molecular , Quassinas/isolamento & purificação , Quassinas/farmacologia , RNA Polimerase Dependente de RNA , Replicação Viral/efeitos dos fármacos , Vírus da Dengue/efeitos dos fármacos
3.
Mar Drugs ; 20(12)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36547933

RESUMO

A global health concern has emerged as a response to the recent SARS-CoV-2 pandemic. The identification and inhibition of drug targets of SARS-CoV-2 is a decisive obligation of scientists. In addition to the cell entry mechanism, SARS-CoV-2 expresses a complicated replication mechanism that provides excellent drug targets. Papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro) play a vital role in polyprotein processing, producing functional non-structural proteins essential for viral replication and survival in the host cell. Moreover, PLpro is employed by SARS-CoV-2 for reversing host immune responses. Therefore, if some particular compound has the potential to interfere with the proteolytic activities of 3CLpro and PLpro of SARS-CoV-2, it may be effective as a treatment or prophylaxis for COVID-19, reducing viral load, and reinstating innate immune responses. Thus, the present study aims to inhibit SARS-CoV-2 through 3CLpro and PLpro using marine natural products isolated from marine algae that contain numerous beneficial biological activities. Molecular docking analysis was utilized in the present study for the initial screening of selected natural products depending on their 3CLpro and PLpro structures. Based on this approach, Ishophloroglucin A (IPA), Dieckol, Eckmaxol, and Diphlorethohydroxycarmalol (DPHC) were isolated and used to perform in vitro evaluations. IPA presented remarkable inhibitory activity against interesting drug targets. Moreover, Dieckol, Eckmaxol, and DPHC also expressed significant potential as inhibitors. Finally, the results of the present study confirm the potential of IPA, Dieckol, Eckmaxol, and DPHC as inhibitors of SARS-CoV-2. To the best of our knowledge, this is the first study that assesses the use of marine natural products as a multifactorial approach against 3CLpro and PLpro of SARS-CoV-2.


Assuntos
Antivirais , COVID-19 , Polifenóis , SARS-CoV-2 , Replicação Viral , Humanos , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , COVID-19/prevenção & controle , Simulação de Acoplamento Molecular , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , Replicação Viral/efeitos dos fármacos , Polifenóis/química , Polifenóis/isolamento & purificação , Polifenóis/farmacologia
4.
J Nat Prod ; 85(11): 2667-2674, 2022 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-36346918

RESUMO

Chromatographic separation on the liquid-state fermented products produced by the fungal strain Alternaria alstroemeriae Km2286 isolated from the littoral medicinal herb Atriplex maximowicziana Makino resulted in the isolation of compounds 1-9. Structures were determined by spectroscopic analysis as four undescribed perylenequinones, altertromins A-D (1-4), along with altertoxin IV (5), altertoxin VIII (6), stemphyperylenol (7), tenuazonic acid (8), and allo-tenuazonic acid (9). Compounds 1-6 exhibited antiviral activities against Epstein-Barr virus (EBV) with EC50 values ranging from 0.17 ± 0.07 to 3.13 ± 0.31 µM and selectivity indices higher than 10. In an anti-neuroinflammatory assay, compounds 1-4, 6, and 7 showed inhibitory activity of nitric oxide production in lipopolysaccharide-induced microglial BV-2 cells, with IC50 values ranging from 0.33 ± 0.04 to 4.08 ± 0.53 µM without significant cytotoxicity. This is the first report to describe perylenequinone-type compounds with potent anti-EBV and anti-neuroinflammatory activities.


Assuntos
Alternaria , Anti-Inflamatórios , Antivirais , Atriplex , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Perileno , Plantas Medicinais , Quinonas , Humanos , Alternaria/química , Alternaria/isolamento & purificação , Atriplex/microbiologia , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/efeitos dos fármacos , Estrutura Molecular , Perileno/química , Perileno/isolamento & purificação , Perileno/farmacologia , Plantas Medicinais/microbiologia , Quinonas/química , Quinonas/isolamento & purificação , Quinonas/farmacologia , Ácido Tenuazônico/química , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia
5.
J Nat Prod ; 85(9): 2135-2141, 2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36075014

RESUMO

The leaf extract of Suregada zanzibariensis gave two new modified ent-abietane diterpenoids, zanzibariolides A (1) and B (2), and two known triterpenoids, simiarenol (3) and ß-amyrin (4). The structures of the isolated compounds were elucidated based on NMR and MS data analysis. Single-crystal X-ray diffraction was used to establish the absolute configurations of compounds 1 and 2. The crude leaf extract inhibited the infectivity of herpes simplex virus 2 (HSV-2, IC50 11.5 µg/mL) and showed toxicity on African green monkey kidney (GMK AH1) cells at CC50 52 µg/mL. The isolated compounds 1-3 showed no anti-HSV-2 activity and exhibited insignificant toxicity against GMK AH1 cells at ≥100 µM.


Assuntos
Abietanos , Antivirais , Suregada , Triterpenos , Abietanos/química , Abietanos/isolamento & purificação , Abietanos/farmacologia , Animais , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Chlorocebus aethiops , Herpesvirus Humano 2/efeitos dos fármacos , Estrutura Molecular , Extratos Vegetais/química , Suregada/química , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
6.
Molecules ; 27(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35268642

RESUMO

Diseases caused by viruses are a global threat, resulting in serious medical and social problems for humanity. They are the main contributors to many minor and major outbreaks, epidemics, and pandemics worldwide. Over the years, medicinal plants have been used as a complementary treatment in a range of diseases. In this sense, this review addresses promising antiviral plants from Marajó island, a part of the Amazon region, which is known to present a very wide biodiversity of medicinal plants. The present review has been limited to articles and abstracts available in Scopus, Web of Science, Science Direct, Scielo, PubMed, and Google Scholar, as well as the patent offices in Brazil (INPI), United States (USPTO), Europe (EPO) and World Intellectual Property Organization (WIPO). As a result, some plants from Marajó island were reported to have actions against HIV-1,2, HSV-1,2, SARS-CoV-2, HAV and HBV, Poliovirus, and influenza. Our major conclusion is that plants of the Marajó region show promising perspectives regarding pharmacological potential in combatting future viral diseases.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Extratos Vegetais/química , Plantas Medicinais/química , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Brasil , COVID-19/virologia , HIV-1/efeitos dos fármacos , Vírus da Hepatite A/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Plantas Medicinais/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação
7.
Mar Drugs ; 20(3)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35323462

RESUMO

The COVID-19 pandemic and its continuing emerging variants emphasize the need to discover appropriate treatment, where vaccines alone have failed to show complete protection against the new variants of the virus. Therefore, treatment of the infected cases is critical. This paper discusses the bio-guided isolation of three indole diketopiperazine alkaloids, neoechinulin A (1), echinulin (2), and eurocristatine (3), from the Red Sea-derived Aspergillus fumigatus MR2012. Neoechinulin A (1) exhibited a potent inhibitory effect against SARS-CoV-2 Mpro with IC50 value of 0.47 µM, which is comparable to the reference standard GC376. Despite the structural similarity between the three compounds, only 1 showed a promising effect. The mechanism of inhibition is discussed in light of a series of extensive molecular docking, classical and steered molecular dynamics simulation experiments. This paper sheds light on indole diketopiperazine alkaloids as a potential structural motif against SARS-CoV-2 Mpro. Additionally, it highlights the potential of different molecular docking and molecular dynamics simulation approaches in the discrimination between active and inactive structurally related Mpro inhibitors.


Assuntos
Antivirais/química , Proteases 3C de Coronavírus/antagonistas & inibidores , Inibidores de Cisteína Proteinase/química , Alcaloides Indólicos/química , Piperazinas/química , SARS-CoV-2/enzimologia , Alcaloides/química , Alcaloides/isolamento & purificação , Antivirais/isolamento & purificação , Aspergillus fumigatus/química , Inibidores de Cisteína Proteinase/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Piperazinas/isolamento & purificação
8.
Mar Drugs ; 20(3)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35323478

RESUMO

Several natural products recovered from a marine-derived Aspergillus niger were tested for their inhibitory activity against SARS CoV-2 in vitro. Aurasperone A (3) was found to inhibit SARS CoV-2 efficiently (IC50 = 12.25 µM) with comparable activity with the positive control remdesivir (IC50 = 10.11 µM). Aurasperone A exerted minimal cytotoxicity on Vero E6 cells (CC50 = 32.36 mM, SI = 2641.5) and it was found to be much safer than remdesivir (CC50 = 415.22 µM, SI = 41.07). To putatively highlight its molecular target, aurasperone A was subjected to molecular docking against several key-viral protein targets followed by a series of molecular dynamics-based in silico experiments that suggested Mpro to be its primary viral protein target. More potent anti-SARS CoV-2 Mpro inhibitors can be developed according to our findings presented in the present investigation.


Assuntos
Antivirais/farmacologia , Cromonas/farmacologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Inibidores de Proteases/farmacologia , SARS-CoV-2/efeitos dos fármacos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Alanina/análogos & derivados , Alanina/farmacologia , Animais , Antivirais/isolamento & purificação , Aspergillus niger/química , Chlorocebus aethiops , Cromonas/isolamento & purificação , Proteases 3C de Coronavírus/metabolismo , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo , Simulação de Acoplamento Molecular , Inibidores de Proteases/isolamento & purificação , RNA Helicases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Vero
9.
Pharm Biol ; 60(1): 509-524, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35234563

RESUMO

CONTEXT: Since the outbreak of SARS-CoV-2, researchers have been working on finding ways to prevent viral entry and pathogenesis. Drug development from naturally-sourced pharmacological constituents may be a fruitful approach to COVID-19 therapy. OBJECTIVE: Most of the published literature has focussed on medicinal plants, while less attention has been given to biodiverse sources such as animal, marine, and microbial products. This review focuses on highlighting natural products and their derivatives that have been evaluated for antiviral, anti-inflammatory, and immunomodulatory properties. METHODS: We searched electronic databases such as PubMed, Scopus, Science Direct and Springer Link to gather raw data from publications up to March 2021, using terms such as 'natural products', marine, micro-organism, and animal, COVID-19. We extracted a number of documented clinical trials of products that were tested in silico, in vitro, and in vivo which paid specific attention to chemical profiles and mechanisms of action. RESULTS: Various classes of flavonoids, 2 polyphenols, peptides and tannins were found, which exhibit inhibitory properties against viral and host proteins, including 3CLpro, PLpro, S, hACE2, and NF-κB, many of which are in different phases of clinical trials. DISCUSSION AND CONCLUSIONS: The synergistic effects of logical combinations with different mechanisms of action emphasizes their value in COVID19 management, such as iota carrageenan nasal spray, ermectin oral drops, omega-3 supplementation, and a quadruple treatment of zinc, quercetin, bromelain, and vitamin C. Though in vivo efficacy of these compounds has yet to be established, these bioproducts are potentially useful in counteracting the effects of SARS-CoV-2.


Assuntos
Antivirais/farmacologia , Produtos Biológicos/farmacologia , Tratamento Farmacológico da COVID-19 , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antivirais/administração & dosagem , Antivirais/isolamento & purificação , Produtos Biológicos/isolamento & purificação , COVID-19/virologia , Desenvolvimento de Medicamentos/métodos , Sinergismo Farmacológico , Humanos , Agentes de Imunomodulação/administração & dosagem , Agentes de Imunomodulação/isolamento & purificação , Agentes de Imunomodulação/farmacologia
10.
Bioengineered ; 13(3): 5480-5508, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35184680

RESUMO

The pandemic of coronavirus disease 2019 (COVID-19) caused by the SARS-coronavirus 2(SARS-CoV-2) virus has become the greatest global public health crisis in recent years,and the COVID-19 epidemic is still continuing. However, due to the lack of effectivetherapeutic drugs, the treatment of corona viruses is facing huge challenges. In thiscontext, countries with a tradition of using herbal medicine such as China have beenwidely using herbal medicine for prevention and nonspecific treatment of corona virusesand achieved good responses. In this review, we will introduce the application of herbalmedicine in the treatment of corona virus patients in China and other countries, andreview the progress of related molecular mechanisms and antiviral activity ingredients ofherbal medicine, in order to provide a reference for herbal medicine in the treatment ofcorona viruses. We found that herbal medicines are used in the prevention and fightagainst COVID-19 in countries on all continents. In China, herbal medicine has beenreported to relieve some of the clinical symptoms of mild patients and shorten the length of hospital stay. However, as most herbal medicines for the clinical treatment of COVID-19still lack rigorous clinical trials, the clinical and economic value of herbal medicines in theprevention and treatment of COVID-19 has not been fully evaluated. Future work basedon large-scale randomized, double-blind clinical trials to evaluate herbal medicines andtheir active ingredients in the treatment of new COVID-19 will be very meaningful.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Medicamentos de Ervas Chinesas/uso terapêutico , Plantas Medicinais/química , SARS-CoV-2/efeitos dos fármacos , Antivirais/isolamento & purificação , COVID-19/patologia , COVID-19/virologia , China , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicina Herbária/métodos , Humanos , Medicina Tradicional Chinesa/métodos , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/patogenicidade
11.
Mar Drugs ; 20(2)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35200645

RESUMO

Herpes simplex virus 1 (HSV-1) remains a prominent health concern widespread all over the world. The increasing genital infections by HSV-1 that might facilitate acquisition and transmission of HIV-1, the cumulative evidence that HSV-1 promotes neurodegenerative disorders, and the emergence of drug resistance signify the need for new antiviral agents. In this study, the in vitro anti-herpetic activity of sulfated polysaccharides (SPs) extracted by enzyme or hot water from seaweeds collected in France and Mexico from stranding events, were evaluated. The anti-herpetic activity evaluation of the semi-refined-polysaccharides (sr-SPs) and different ion exchange purified fractions showed a wide range of antiviral activity. Among them, the sr-SPs from the Rhodophyta Halymenia floresii showed stronger activity EC50 0.68 µg/mL with SI 1470, without cytotoxicity. Further, the antiviral activity of the sr-SPs evaluated at different treatment schemes showed a high EC50 of 0.38 µg/mL during the viral adsorption assays when the polysaccharide and the virus were added simultaneously, whilst the protection on Vero cell during the post-infection assay was effective up to 1 h. The chemical composition, FTIR and 1H NMR spectroscopic, and molecular weights of the sr-SPs from H. floresii were determined and discussed based on the anti-herpetic activity. The potential utilization of seaweed stranding as a source of antiviral compounds is addressed.


Assuntos
Antivirais/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Polissacarídeos/farmacologia , Alga Marinha/química , Animais , Antivirais/isolamento & purificação , Chlorocebus aethiops , França , México , Peso Molecular , Polissacarídeos/isolamento & purificação , Sulfatos , Células Vero
12.
Mar Drugs ; 20(2)2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35200660

RESUMO

Human noroviruses are the most common pathogens causing acute gastroenteritis and may lead to more severe illnesses among immunosuppressed people, including elderly and organ transplant recipients. To date, there are no safe and effective vaccines or antiviral agents for norovirus infections. In the present study, we aimed to demonstrate the antiviral activity of monogalactosyl diacylglyceride (MGDG) isolated from a microalga, Coccomyxa sp. KJ, against murine norovirus (MNV) and feline calicivirus (FCV), the surrogates for human norovirus. MGDG showed virucidal activities against these viruses in a dose- and time-dependent manner-MGDG at 100 µg/mL reduced the infectivity of MNV and FCV to approximately 10% after 60 min incubation. In the animal experiments of MNV infection, intraoral administration of MGDG (1 mg/day) exerted a therapeutic effect by suppressing viral shedding in the feces and produced high neutralizing antibody titers in sera and feces. When MGDG was orally administered to immunocompromised mice treated with 5-fluorouracil, the compound exhibited earlier stopping of viral shedding and higher neutralizing antibody titers of sera than those in the control mice administered with distilled water. Thus, MGDG may offer a new therapeutic and prophylactic alternative against norovirus infections.


Assuntos
Antivirais/farmacologia , Infecções por Caliciviridae/tratamento farmacológico , Galactolipídeos/farmacologia , Microalgas/metabolismo , Animais , Anticorpos Neutralizantes/sangue , Antivirais/administração & dosagem , Antivirais/isolamento & purificação , Infecções por Caliciviridae/virologia , Calicivirus Felino/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Galactolipídeos/administração & dosagem , Galactolipídeos/isolamento & purificação , Camundongos , Camundongos Endogâmicos BALB C , Norovirus/efeitos dos fármacos , Fatores de Tempo , Eliminação de Partículas Virais/efeitos dos fármacos
13.
Artigo em Inglês | MEDLINE | ID: mdl-35007897

RESUMO

Yellow catfish (Pelteobagrus fulvidraco) is commonly contaminated by protease inhibitors because of the illegal use of antiviral drugs in aquaculture, so the determination of antiviral drugs is essential in food safety supervision. In this study, a novel sorbent, graphene and silica nanospheres composite (G/KCC-1), was synthesized for pipette-tip-based solid-phase extraction (PT-SPE) and purification of ritonavir, saquinavir, and indinavir in yellow catfish, followed by ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS) analysis. The wrinkly structure of G/KCC-1 with center-radial nanowrinkles enlarged the surface area and increased the capacity of absorbing the target analyte. With the proposed G/KCC-1 based PT-SPE UPLC-MS/MS method, the pH of sample solution, aspirating/dispensing cycles for extraction and elution were optimized to be 4.0, 25, and 10 respectively, and the eluting solvent was methanol/ammonia (95:5, v/v) with 0.02 M sodium chloride. This new method was further validated to be linear (correlation coefficient R2, 0.9993-0.9996), sensitive (limit of detection, LOD ≤ 0.8 ng mL-1), accurate (89.3-114.2%), and precise (relative standard deviation, RSD ≤ 6.23%). These results indicated that the proposed method is qualified in bioanalytical method validation and meets the requirements for detecting illegally used antiviral drugs in yellow catfish. The demonstrated G/KCC-1 based PT-SPE UPLC-MS/MS method is a potential analytical method in food and drug administration.


Assuntos
Antivirais/análise , Peixes-Gato , Cromatografia Líquida de Alta Pressão/métodos , Nanosferas/química , Extração em Fase Sólida/métodos , Animais , Antivirais/isolamento & purificação , Aquicultura , Grafite/química , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Dióxido de Silício/química , Espectrometria de Massas em Tandem/métodos
14.
Int J Mol Sci ; 23(2)2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35055133

RESUMO

Herpesviruses are highly prevalent in the human population, and frequent reactivations occur throughout life. Despite antiviral drugs against herpetic infections, the increasing appearance of drug-resistant viral strains and their adverse effects prompt the research of novel antiherpetic drugs for treating lesions. Peptides obtained from natural sources have recently become of particular interest for antiviral therapy applications. In this work, we investigated the antiviral activity of the peptide A-3302-B, isolated from a marine bacterium, Micromonospora sp., strain MAG 9-7, against herpes simplex virus type 1, type 2, and human cytomegalovirus. Results showed that the peptide exerted a specific inhibitory activity against HSV-2 with an EC50 value of 14 µM. Specific antiviral assays were performed to investigate the mechanism of action of A-3302-B. We demonstrated that the peptide did not affect the expression of viral proteins, but it inhibited the late events of the HSV-2 replicative cycle. In detail, it reduced the cell-to-cell virus spread and the transmission of the extracellular free virus by preventing the egress of HSV-2 progeny from the infected cells. The dual antiviral and previously reported anti-inflammatory activities of A-3302-B, and its effect against an acyclovir-resistant HSV-2 strain are attractive features for developing a therapeutic to reduce the transmission of HSV-2 infections.


Assuntos
Antivirais/farmacologia , Herpesvirus Humano 2/fisiologia , Micromonospora/química , Peptídeos/farmacologia , Animais , Antivirais/química , Antivirais/isolamento & purificação , Chlorocebus aethiops , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/fisiologia , Prepúcio do Pênis/citologia , Prepúcio do Pênis/virologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 2/efeitos dos fármacos , Humanos , Masculino , Estrutura Molecular , Peptídeos/química , Peptídeos/isolamento & purificação , Células Vero , Liberação de Vírus/efeitos dos fármacos
15.
Artigo em Inglês | MEDLINE | ID: mdl-34974319

RESUMO

Favipiravir is a promising antiviral agent that has been recently approved for treatment of COVID-19 infection. In this study, a menthol-assisted homogenous liquid-liquid microextraction method has been developed for favipiravir determination in human plasma using HPLC/UV. The different factors that could affect the extraction efficiency were studied, including extractant type, extractant volume, menthol amount and vortex time. The optimum extraction efficiency was achieved using 300 µL of tetrahydrofuran, 30 mg of menthol and vortexing for 1 min before centrifuging the sample for 5 min at 3467g. Addition of menthol does not only induce phase separation, but also helps to form reverse micelles to facilitate extraction. The highly polar favipiravir molecules would be incorporated into the hydrophilic core of the formed reverse micelle to be extracted by the non-polar organic extractant. The method was validated according to the FDA bioanalytical method guidelines. The developed method was found linear in the concentration range of 0.1 to 100 µg/mL with a coefficient of determination of 0.9992. The method accuracy and precision were studied by calculating the recovery (%) and the relative standard deviation (%), respectively. The recovery (%) was in the range of 97.1-103.9%, while the RSD (%) values ranged between 2.03 and 8.15 %. The developed method was successfully applied in a bioequivalence study of Flupirava® 200 mg versus Avigan® 200 mg, after a single oral dose of favipiravir administered to healthy adult volunteers. The proposed method was simple, cheap, more eco-friendly and sufficiently sensitive for biomedical application.


Assuntos
Amidas/isolamento & purificação , Antivirais/isolamento & purificação , Tratamento Farmacológico da COVID-19 , Microextração em Fase Líquida/métodos , Pirazinas/isolamento & purificação , Amidas/administração & dosagem , Amidas/sangue , Antivirais/administração & dosagem , Antivirais/sangue , COVID-19/sangue , COVID-19/virologia , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Microextração em Fase Líquida/instrumentação , Mentol/química , Pirazinas/administração & dosagem , Pirazinas/sangue , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia
16.
Molecules ; 28(1)2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36615236

RESUMO

Screening of the antiviral and virucidal activities of ethanol extracts from plants endemic to the Republic of Korea revealed the inhibitory activity of a 70% ethanol extract of the whole plant of A. pseudoglehnii (APE) against influenza virus infection. Two chlorophyll derivatives, ethyl pheophorbides a and b, isolated as active components of APE, exerted virucidal effects with no evident cytotoxicity. These compounds were effective only under conditions of direct incubation with the virus, and exerted no effects on the influenza A virus (IAV) surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). Interestingly, virucidal activities of ethyl pheophorbides a and b were observed against enveloped but not non-enveloped viruses, suggesting that these compounds act by affecting the integrity of the viral membrane and reducing infectivity.


Assuntos
Antivirais , Aster , Vírus da Influenza A , Animais , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Etanol/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Vírus da Influenza A/efeitos dos fármacos , Neuraminidase , Aster/química , Cães , Células Madin Darby de Rim Canino
17.
J Ethnopharmacol ; 287: 114951, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-34958877

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Elaeocarpus sylvestris var. ellipticus (ES), a plant that grows in Taiwan, Japan, and Jeju Island in Korea. ES root bark, known as "sanduyoung," has long been used in traditional oriental medicine. ES is also traditionally used to treat anxiety, asthma, arthritis, stress, depression, palpitation, nerve pain, epilepsy, migraine, hypertension, liver diseases, diabetes, and malaria. However, lack of efficacy and mechanism studies on ES. AIM OF THE STUDY: In the present study, we aim to investigate the VZV-antiviral efficacy, pain suppression, and the anti-inflammatory and antipyretic effects of ES. METHODS: and methods: Inhibition of VZV was evaluated by hollow fiber assays. Analgesic and antipyretic experiments were conducted using ICR mice and SD Rats, and anti-inflammatory experiments were conducted using Raw264.7 cells. RESULTS: To evaluate the efficacy of ESE against VZV, we conducted antiviral tests. ESE inhibited cell death by disrupting virus and gene expression related to invasion and replication. In addition, ESE suppressed the pain response as measured by writhing and formalin tests and suppressed LPS-induced inflammatory fever. Further, ESE inhibited the phosphorylation of IκB and NF-κB in LPS-induced Raw264.7 cells and expression of COX-2, iNOS, IL-1ß, IL-6, and TNF-α. CONCLUSION: E. sylvestris shows potential as a source of medicine. ESE had a direct effect on VZV and an inhibitory effect on the pain and inflammation caused by VZV infection.


Assuntos
Antivirais/farmacologia , Elaeocarpaceae/química , Herpesvirus Humano 3/efeitos dos fármacos , Extratos Vegetais/farmacologia , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antipiréticos/isolamento & purificação , Antipiréticos/farmacologia , Antivirais/isolamento & purificação , Inflamação/tratamento farmacológico , Inflamação/virologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Dor/tratamento farmacológico , Dor/virologia , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológico , Infecção pelo Vírus da Varicela-Zoster/virologia
18.
Biomed Pharmacother ; 146: 112507, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34891122

RESUMO

Lectins or clusters of carbohydrate-binding proteins of non-immune origin are distributed chiefly in the Plantae. Lectins have potent anti-infectivity properties for several RNA viruses including SARS-CoV-2. The primary purpose of this review is to review the ability of lectins mediated potential biotherapeutic and bioprophylactic strategy against coronavirus causing COVID-19. Lectins have binding affinity to the glycans of SARS-COV-2 Spike glycoprotein that has N-glycosylation sites. Apart from this, the complement lectin pathway is a "first line host defense" against the viral infection that is activated by mannose-binding lectins. Mannose-binding lectins deficiency in serum influences innate immunity of the host and facilitates infectious diseases including COVID-19. Our accumulated evidence obtained from scientific databases particularly PubMed and Google Scholar databases indicate that mannose-specific/mannose-binding lectins (MBL) have potent efficacies like anti-infectivity, complement cascade induction, immunoadjuvants, DC-SIGN antagonists, or glycomimetic approach, which can prove useful in the strategy of COVID-19 combat along with the glycobiological aspects of SARS-CoV-2 infections and antiviral immunity. For example, plant-derived mannose-specific lectins BanLac, FRIL, Lentil, and GRFT from red algae can inhibit and neutralize SARS-CoV-2 infectivity, as confirmed with in-vitro, in-vivo, and in-silico assessments. Furthermore, Bangladesh has a noteworthy resource of antiviral medicinal plants as well as plant lectins. Intensifying research on the antiviral plant lectins, adopting a glyco-biotechnological approach, and with deeper insights into the "glycovirological" aspects may result in the designing of alternative and potent blueprints against the 21st century's biological pandemic of SARS-CoV-2 causing COVID-19.


Assuntos
Antivirais/uso terapêutico , Terapia Biológica/métodos , COVID-19/prevenção & controle , Erradicação de Doenças/métodos , Lectinas de Plantas/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Animais , Antivirais/isolamento & purificação , Antivirais/farmacologia , Terapia Biológica/tendências , COVID-19/epidemiologia , Erradicação de Doenças/tendências , Humanos , Lectinas de Plantas/isolamento & purificação , Lectinas de Plantas/farmacologia
19.
Chem Biodivers ; 19(1): e202100668, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34812586

RESUMO

Forsyqinlingines C (1) and D (2), two C9 -monoterpenoid alkaloids bearing a rare skeleton, were isolated from the ripe fruits of Forsythia suspensa. Their structures, including absolute configurations, were fully elucidated by extensive spectroscopic data and ECD experiments. The plausible biogenetic pathway for compounds 1 and 2 was also proposed. In vitro, two C9 -monoterpenoid alkaloids showed anti-inflammatory activity performed by the inhibitory effect on the release of ß-glucuronidase in rat polymorphonuclear leukocytes (PMNs), as well as antiviral activity against influenza A (H1N1) virus and respiratory syncytial virus (RSV).


Assuntos
Alcaloides/química , Anti-Inflamatórios/química , Antivirais/química , Forsythia/química , Monoterpenos/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antivirais/isolamento & purificação , Antivirais/farmacologia , Forsythia/metabolismo , Frutas/química , Frutas/metabolismo , Glucuronidase/metabolismo , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Fator de Ativação de Plaquetas/farmacologia , Ratos , Vírus Sinciciais Respiratórios/efeitos dos fármacos
20.
Bioorg Chem ; 119: 105567, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34971945

RESUMO

Twenty-four racemic acylphloroglucinol meroterpenoids including eighteen unusual stuctures (3 âˆ¼ 10, 13, 14, and 17 âˆ¼ 24), and a major component filixic acid ABA (25), were isolated from Dryopteris crassirhizoma. Structurally, the dimeric acylphloroglucinol derivatives possess unprecedented skeletons of mixed acylphloroglucinol and sesquiterpene biosynthetic origin. The stereochemistries of six reported meroterpenoids with undefined chiral centers were reassigned. Two intriguing methods by analyzing a) the regularity of chemical shift variation of protons and carbons around the stereogenic centers, and b) pyridine-induced deshielding effect of hydroxy groups, to discriminate relative configurations of flexible long-chain alcohol with chiral centers separated by three or seven covalent bonds, were successfully applied. A non-enzymatic biosynthesis of 1 âˆ¼ 24 was assumed based on a rare single-crystal cluster formed with two diastereomeric enantiomer pairs (±1/±2) and chiral HPLC analyses. Meroterpenoids 13 and 14 showed obvious inhibitory effects on NO production in LPS-induced RAW264.7, and suppressed the expression of iNOS, COX-2, IL-1ß, and IL-18. Their anti-inflammatory activity was closely related to the inhibition of the formation and function of inflammasomes. Additionally, the known 25 showed antiviral efficacy against the influenza viruse A/Puerto Rico/8/1934 (H1N1).


Assuntos
Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Dryopteris/química , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Floroglucinol/farmacologia , Terpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antivirais/química , Antivirais/isolamento & purificação , Relação Dose-Resposta a Droga , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Floroglucinol/química , Floroglucinol/isolamento & purificação , Células RAW 264.7 , Estereoisomerismo , Relação Estrutura-Atividade , Terpenos/química , Terpenos/isolamento & purificação
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