Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.455
Filtrar
1.
Cardiovasc Pathol ; 49: 107260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32683240

RESUMO

PURPOSE: to study the effect of immunosupressive therapy (IST) in the virus-negative and virus-positive patients with immune-mediated myocarditis. METHODS: in 60 patients (45 male, 46.7 ± 11.8 years, mean LV EDD, 6.7 ± 0.7 cm, EF 26.2 ± 9.1%) active/borderline myocarditis was verified by endomyocardial biopsy (n = 38), intraoperative biopsy (n = 10), examination of explanted heart (n = 3) and autopsy (n = 9). Indications for IST determined based on histological, immune activity. The follow-up was 19.0 [7.25; 40.25] months. RESULTS: The viral genome in the myocardium was detected in 32 patients (V+ group), incl. parvovirus B19 in 23. The anti-heart antibody level was equally high in the V+ and V- patients. Antiviral therapy was administered in 24 patients. IST (in 22 V+ and 24 V- patients) include steroids (n = 40), hydroxychloroquine (n = 20), azathioprine (n = 21). The significant decrease of LV EDD (6.7 ± 0.7 to 6.4 ± 0.8), PAP (48.9 ± 15.5 to 39.4 ± 11.5 mm Hg, р<0,01), increase of EF (26.5 ± 0.9 to 36.0 ± 10.8), and lower lethality (23.9% and 64.3%; RR 0.37, 95% CI 0.19-0.71), p<0.01, were found only in IST group. Significant improvement due to IST were achieved not only in V-, but also in V+ patients. CONCLUSIONS: IST in patients with immune-mediated lymphocytic myocarditis is effective and is associated with lower lethality both in virus-negative and virus-positive patients.


Assuntos
Antivirais/uso terapêutico , Autoanticorpos/sangue , Imunossupressores/uso terapêutico , Linfócitos/efeitos dos fármacos , Miocardite/tratamento farmacológico , Miocárdio/imunologia , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacos , Adulto , Idoso , Biópsia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Linfócitos/imunologia , Linfócitos/patologia , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Miocardite/imunologia , Miocardite/patologia , Miocardite/virologia , Miocárdio/patologia , Resultado do Tratamento , Viroses/imunologia , Viroses/patologia , Viroses/virologia , Vírus/imunologia , Adulto Jovem
2.
Arch Microbiol ; 202(9): 2569-2578, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32671418

RESUMO

This study screened mastic gum (Pistacia lentiscus L.) for antiviral activity against herpes simplex virus type 2 (HSV-2), coxsackievirus type B3, and adenovirus type 5. The organs of this plant (leaves, stem, and seed) were macerated sequentially using solvents of increasing polarity (hexane, dichloromethane, ethyl acetate, and methanol). Only the methanol extract of stem exhibited significant activity against HSV-2. This extract showed anti-HSV-2 activity with a selectivity index of 51 (50% cytotoxic concentration = 186 µg/mL; 50% inhibitory concentration = 3.63 µg/mL), and demonstrated direct inhibition against this virus with a virucidal selectivity index of 620 (50% virucidal concentration = 0.30 µg/mL). A bio-guided assay involving thin-layer chromatography led to the isolation of two active compounds, which have been identified as dammaradienone and dammaradienol using high-performance liquid chromatography-diode array detection coupled with electrospray ionization mass spectrometry. P. lentiscus has been widely studied for other biological activities. However, to our knowledge, this is the first report of P. lentiscus L. exhibiting antiviral activity.


Assuntos
Pistacia/química , Extratos Vegetais/farmacologia , Vírus/efeitos dos fármacos , Adenoviridae/efeitos dos fármacos , Antivirais/química , Antivirais/farmacologia , Cromatografia Líquida de Alta Pressão , Enterovirus/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Folhas de Planta/química , Sementes/química , Solventes/química
3.
Scand J Immunol ; 92(3): e12928, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32640050

RESUMO

Several enveloped viruses, particularly some RNA viruses, have high rates of mutation or replication, which can make them virulent pathogens in humans and other mammals. A proposed treatment could use synthesized proteins to mask pathogenic viral surface proteins to quickly induce an immune attack on specific enveloped viruses by using existing immune cells. One treatment could inject dual-protein ligand masks into patients' bloodstreams to mask pathogenic surface proteins used to infect mammalian cells. The mammalian immune system already uses an analogous, more complex structure called a pentraxin to neutralize some pathogens by connecting their surface proteins to immune cells. And several types of antiviral peptides have already experimentally demonstrated effectiveness in blocking various viral pathogen infections. These treatments offer advantages, especially for currently untreatable viral pathogens. Furthermore, using dual-protein ligands and the antigenic memory of some sub-populations of NK cells would also allow the creation of defacto vaccines based on a host's NK cells, instead of vaccines utilizing CD4 and CD8 α:ß T cells, which are limited by the requirement of MHC presentation of the target antigens to α:ß T cells. Targeted NK cell vaccines could attack host cells latently or actively infected by intracellular pathogens, even host cells having pathogen downregulated MHC antigen presentation. Eight postulates concerning the effects of pathogen mutation, or change in phenotype from genetic recombination or rearrangement, and replication rates on pathogen vs host dominance are also listed, which should be applicable to viral and non-viral pathogens.


Assuntos
Mutação , Viroses/virologia , Fenômenos Fisiológicos Virais , Replicação Viral , Vírus/genética , Antivirais/farmacologia , Antivirais/uso terapêutico , Interações Hospedeiro-Patógeno/imunologia , Humanos , Taxa de Mutação , Fenótipo , Recombinação Genética , Viroses/tratamento farmacológico , Viroses/imunologia , Vírus/efeitos dos fármacos , Vírus/imunologia
4.
Arch Virol ; 165(9): 1935-1945, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32594322

RESUMO

Plants are a rich source of new antiviral, pharmacologically active agents. The naturally occurring plant alkaloid berberine (BBR) is one of the phytochemicals with a broad range of biological activity, including anticancer, anti-inflammatory and antiviral activity. BBR targets different steps in the viral life cycle and is thus a good candidate for use in novel antiviral drugs and therapies. It has been shown that BBR reduces virus replication and targets specific interactions between the virus and its host. BBR intercalates into DNA and inhibits DNA synthesis and reverse transcriptase activity. It inhibits replication of herpes simplex virus (HSV), human cytomegalovirus (HCMV), human papillomavirus (HPV), and human immunodeficiency virus (HIV). This isoquinoline alkaloid has the ability to regulate the MEK-ERK, AMPK/mTOR, and NF-κB signaling pathways, which are necessary for viral replication. Furthermore, it has been reported that BBR supports the host immune response, thus leading to viral clearance. In this short review, we focus on the most recent studies on the antiviral properties of berberine and its derivatives, which might be promising agents to be considered in future studies in the fight against the current pandemic SARS-CoV-2, the virus that causes COVID-19.


Assuntos
Antivirais/farmacologia , Berberina/farmacologia , Vírus/efeitos dos fármacos , Animais , Antivirais/química , Berberina/química , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Viroses/virologia , Replicação Viral/efeitos dos fármacos , Vírus/genética , Vírus/crescimento & desenvolvimento
5.
mBio ; 11(3)2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32371599

RESUMO

The vaginal microbiota influences sexual transmission of human immunodeficiency virus type 1 (HIV-1). Colonization of the vaginal tract is normally dominated by Lactobacillus species. Both Lactobacillus and Enterococcus faecalis may secrete reutericyclin, which inhibits the growth of a variety of pathogenic bacteria. Increasing evidence suggests a potential therapeutic role for an analogue of reutericyclin, glycerol monolaurate (GML), against microbial pathogens. Previous studies using a macaque vaginal simian immunodeficiency virus (SIV) transmission model demonstrated that GML reduces transmission and alters immune responses to infection in vitro Previous studies showed that structural analogues of GML negatively impact other enveloped viruses. We sought to expand understanding of how GML inhibits HIV-1 and other enveloped viruses and show that GML restricts HIV-1 entry post-CD4 engagement at the step of coreceptor binding. Further, HIV-1 and yellow fever virus (YFV) particles were more sensitive to GML interference than particles "matured" by proteolytic processing. We show that high-pressure-liquid-chromatography (HPLC)-purified reutericyclin and reutericyclin secreted by Lactobacillus inhibit HIV-1. These data emphasize the importance and protective nature of the normal vaginal flora during viral infections and provide insights into the antiviral mechanism of GML during HIV-1 infection and, more broadly, to other enveloped viruses.IMPORTANCE A total of 340 million sexually transmitted infections (STIs) are acquired each year. Antimicrobial agents that target multiple infectious pathogens are ideal candidates to reduce the number of newly acquired STIs. The antimicrobial and immunoregulatory properties of GML make it an excellent candidate to fit this critical need. Previous studies established the safety profile and antibacterial activity of GML against both Gram-positive and Gram-negative bacteria. GML protected against high-dose SIV infection and reduced inflammation, which can exacerbate disease, during infection. We found that GML inhibits HIV-1 and other human-pathogenic viruses (yellow fever virus, mumps virus, and Zika virus), broadening its antimicrobial range. Because GML targets diverse infectious pathogens, GML may be an effective agent against the broad range of sexually transmitted pathogens. Further, our data show that reutericyclin, a GML analog expressed by some lactobacillus species, also inhibits HIV-1 replication and thus may contribute to the protective effect of Lactobacillus in HIV-1 transmission.


Assuntos
Antivirais/farmacologia , Lactobacillus/metabolismo , Lauratos/farmacologia , Monoglicerídeos/farmacologia , Proteínas do Envelope Viral/metabolismo , Vírus/efeitos dos fármacos , Animais , Antivirais/metabolismo , Feminino , HIV-1/efeitos dos fármacos , HIV-1/metabolismo , HIV-1/fisiologia , Humanos , Lauratos/metabolismo , Monoglicerídeos/metabolismo , Receptores Virais/metabolismo , Ácido Tenuazônico/análogos & derivados , Ácido Tenuazônico/metabolismo , Ácido Tenuazônico/farmacologia , Vagina/microbiologia , Ligação Viral , Internalização do Vírus , Vírus/metabolismo
6.
Mar Drugs ; 18(4)2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32331442

RESUMO

The enzymatic depolymerization of fucoidans from brown algae allowed the production of their standardized derivatives with different biological activities. This work aimed to compare the antiviral activities of native (FeF) and modified with enzyme (FeHMP) fucoidans from F. evanescens. The cytotoxicity and antiviral activities of the FeF and FeHMP against herpes viruses (HSV-1, HSV-2), enterovirus (ECHO-1), and human immunodeficiency virus (HIV-1) in Vero and human MT-4 cell lines were examined by methylthiazolyltetrazolium bromide (MTT) and cytopathic effect (CPE) reduction assays, respectively. The efficacy of fucoidans in vivo was evaluated in the outbred mice model of vaginitis caused by HSV-2. We have shown that both FeF and FeHMP significantly inhibited virus-induced CPE in vitro and were more effective against HSV. FeF exhibited antiviral activity against HSV-2 with a selective index (SI) > 40, and FeHMP with SI ˃ 20, when they were added before virus infection or at the early stages of the HSV-2 lifecycle. Furthermore, in vivo studies showed that after intraperitoneal administration (10 mg/kg), both FeF and FeHMP protected mice from lethal intravaginal HSV-2 infection to approximately the same degree (44-56%). Thus, FeF and FeHMP have comparable potency against several DNA and RNA viruses, allowing us to consider the studied fucoidans as promising broad-spectrum antivirals.


Assuntos
Antivirais/farmacologia , Fucus/química , Polissacarídeos/farmacologia , Vírus/efeitos dos fármacos , Animais , Antivirais/isolamento & purificação , Chlorocebus aethiops , Vírus de DNA/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Polissacarídeos/isolamento & purificação , Vírus de RNA/efeitos dos fármacos , Vaginite/tratamento farmacológico , Vaginite/virologia , Células Vero
8.
Viruses ; 12(3)2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204464

RESUMO

Cats are becoming more popular as household companions and pets, forming close relationships with humans. Although feline viral diseases can pose serious health hazards to pet cats, commercialized preventative vaccines are lacking. Interferons (IFNs), especially type I IFNs (IFN-α, IFN-ß, and interferon omega (IFN-ω)), have been explored as effective therapeutic drugs against viral diseases in cats. Nevertheless, there is limited knowledge regarding feline IFN-ω (feIFN-ω), compared to IFN-α and IFN-ß. In this study, we cloned the genes encoding feIFN-ωa and feIFN-ωb from cat spleen lymphocytes. Homology and phylogenetic tree analysis revealed that these two genes belonged to new subtypes of feIFN-ω. The recombinant feIFN-ωa and feIFN-ωb proteins were expressed in their soluble forms in Escherichia coli, followed by purification. Both proteins exhibited effective anti-vesicular stomatitis virus (VSV) activity in Vero, F81 (feline kidney cell), Madin-Darby bovine kidney (MDBK), Madin-Darby canine kidney (MDCK), and porcine kidney (PK-15) cells, showing broader cross-species antiviral activity than the INTERCAT IFN antiviral drug. Furthermore, the recombinant feIFN-ωa and feIFN-ωb proteins demonstrated antiviral activity against VSV, feline coronavirus (FCoV), canine parvovirus (CPV), bovine viral diarrhea virus (BVDV), and porcine epidemic diarrhea virus (PEDV), indicating better broad-spectrum antiviral activity than the INTERCAT IFN. The two novel feIFN-ω proteins (feIFN-ωa and feIFN-ωb) described in this study show promising potential to serve as effective therapeutic agents for treating viral infections in pet cats.


Assuntos
Antivirais/farmacologia , Interferon Tipo I/genética , Interferon Tipo I/farmacologia , Sequência de Aminoácidos , Animais , Antivirais/isolamento & purificação , Sequência de Bases , Gatos , Bovinos , Linhagem Celular , Chlorocebus aethiops , Clonagem Molecular , Cães , Escherichia coli/genética , Escherichia coli/metabolismo , Interferon Tipo I/química , Interferon Tipo I/metabolismo , Filogenia , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Suínos , Células Vero , Vírus/classificação , Vírus/efeitos dos fármacos
9.
Subcell Biochem ; 94: 63-80, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189296

RESUMO

Anti-lipopolysaccharide factors (ALFs) are a type of antimicrobial peptide (AMP) which show broad-spectrum antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, fungi and viruses. In this chapter, we review the discovery and classification of this kind of antimicrobial peptide in crustaceans. The structure and function, as well as the mechanism of antibacterial and antiviral activities of ALFs will be summarized and discussed. We will then describe the expression and regulation of various ALF genes in different crustacean species. Finally, the application prospects of ALFs in drug development and disease-resistant genetic breeding will be pointed out and discussed. The review will also discuss several key questions such as the systematic classification and expression regulation of the ALF genes, as well as the future application of ALFs and ALF-derived peptides.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Proteínas de Artrópodes/farmacologia , Crustáceos , Animais , Bactérias/efeitos dos fármacos , Crustáceos/genética , Crustáceos/microbiologia , Crustáceos/virologia , Desenvolvimento de Medicamentos , Fungos/efeitos dos fármacos , Lipopolissacarídeos , Vírus/efeitos dos fármacos
11.
Planta ; 251(3): 70, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32086615

RESUMO

MAIN CONCLUSION: Lipopeptides could help to overcome a large concern in agriculture: resistance against chemical pesticides. These molecules have activity against various phytopathogens and a potential to be transformed by genetic engineering. The exponential rise of pest resistances to different chemical pesticides and the global appeal of consumers for a sustainable agriculture and healthy nutrition have led to the search of new solutions for pest control. Furthermore, new laws require a different stance of producers. Based on that, bacteria of the genus Bacillus present a great agricultural potential, producing lipopeptides (LPs) that have high activity against insects, mites, nematodes, and/or phytopathogens that are harmful to plant cultures. Biopesticide activity can be found mainly in three families of Bacillus lipopeptides: surfactin, iturin, and fengycin. These molecules have an amphiphilic nature, interfering with biological membrane structures. Their antimicrobial properties include activity against bacteria, fungi, oomycetes, and viruses. Recent studies also highlight the ability of these compounds to stimulate defense mechanisms of plants and biofilm formation, which is a key factor for the successful colonization of biocontrol organisms. The use of molecular biology has also recently been researched for continuous advances and discoveries of new LPs, avoiding possible future problems of resistance against these molecules. As a consequence of the properties and possibilities of LPs, numerous studies and developments as well as the attention of large companies in the field is expected in the near future.


Assuntos
Agricultura , Bacillus/metabolismo , Lipopeptídeos/farmacologia , Controle Biológico de Vetores/métodos , Animais , Anti-Infecciosos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Resistência a Medicamentos , Fungos/efeitos dos fármacos , Insetos/efeitos dos fármacos , Lipopeptídeos/química , Lipopeptídeos/metabolismo , Ácaros/efeitos dos fármacos , Nematoides/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Praguicidas/farmacologia , Doenças das Plantas/prevenção & controle , Plantas/microbiologia , Vírus/efeitos dos fármacos
12.
Curr Top Med Chem ; 20(3): 244-255, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995008

RESUMO

4-Oxoquinoline derivatives constitute an important family of biologically important substances, associated with different bioactivities, which can be synthesized by different synthetic methods, allowing the design and preparation of libraries of substances with specific structural variations capable of modulating their pharmacological action. Over the last years, these substances have been extensively explored by the scientific community in efforts to develop new biologically active agents, with greater efficiency for the treatment of a variety of diseases. Viral infections have been one of the targets of these studies, although to a lesser extent than other diseases such as cancer and bacterial infections. Nevertheless, the literature provides examples that corroborate with the fact that these substances may act on different pharmacological targets in different viral pathogens. This review provides a compilation of some of the major studies published in recent years showing the discovery and/or development of new antiviral oxoquinoline agents, highlighting, whenever possible, their mechanisms of action.


Assuntos
4-Quinolonas/farmacologia , Antivirais/farmacologia , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacos , 4-Quinolonas/síntese química , 4-Quinolonas/química , Antivirais/síntese química , Antivirais/química , Desenvolvimento de Medicamentos , Humanos , Estrutura Molecular
13.
J Biol Chem ; 295(6): 1694-1703, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-31914414

RESUMO

Small-molecule inhibitors of translation are critical tools to study the molecular mechanisms of protein synthesis. In this study, we sought to characterize how QL47, a host-targeted, small-molecule antiviral agent, inhibits steady-state viral protein expression. We demonstrate that this small molecule broadly inhibits both viral and host protein synthesis and targets a translation step specific to eukaryotic cells. We show that QL47 inhibits protein neosynthesis initiated by both canonical cap-driven and noncanonical initiation strategies, most likely by targeting an early step in translation elongation. Our findings thus establish QL47 as a new small-molecule inhibitor that can be utilized to probe the eukaryotic translation machinery and that can be further developed as a new therapeutic agent.


Assuntos
Antivirais/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Antivirais/química , Linhagem Celular , Células HEK293 , Humanos , Proteínas/metabolismo , Bibliotecas de Moléculas Pequenas/química , Proteínas Virais/metabolismo , Viroses/tratamento farmacológico , Viroses/metabolismo , Vírus/efeitos dos fármacos , Vírus/metabolismo
14.
Adv Exp Med Biol ; 1217: 99-110, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31898224

RESUMO

Cullin-RING ubiquitin ligases (CRLs) are efficient and diverse toolsets of the cells to regulate almost every biological process. However, these characteristics have also been usurped by many viruses to optimize for their replication. CRLs are often at the forefront of the arms races in the coevolution of viruses and hosts. Here we review the modes of actions and functional consequences of viral manipulations of host cell CRLs. We also discuss the therapeutic applications to target these viral manipulations for treating viral infections.


Assuntos
Proteínas Culina/metabolismo , Interações Hospedeiro-Patógeno , Viroses/metabolismo , Viroses/virologia , Vírus/metabolismo , Evolução Biológica , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Viroses/tratamento farmacológico , Replicação Viral/efeitos dos fármacos , Vírus/efeitos dos fármacos , Vírus/crescimento & desenvolvimento
15.
Eur J Clin Microbiol Infect Dis ; 39(1): 5-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31422545

RESUMO

Despite tremendous advances in the development of anti-viral therapeutics, viral infections remain a chief culprit accounting for ongoing morbidity and mortality worldwide. Natural products, in particular animal venoms, embody a veritable cornucopia of exotic constituents, suggesting an immensurable source of anti-infective drugs. In this context, melittin, the principal constituent in the venom of the European honeybee Apis mellifera, has been demonstrated to exert anti-cancer, anti-inflammatory, anti-diabetic, anti-infective, and adjuvant properties. To our knowledge, there is no review appertaining to effects of melittin against viruses, prompting us to synopsize experimental investigations on its anti-viral activity throughout the past decades. Accumulating evidence indicates that melittin curbs infectivity of a diverse array of viruses including coxsackievirus, enterovirus, influenza A viruses, human immunodeficiency virus (HIV), herpes simplex virus (HSV), Junín virus (JV), respiratory syncytial virus (RSV), vesicular stomatitis virus (VSV), and tobacco mosaic virus (TMV). However, medication safety, different routes of administrations, and molecular mechanisms behind the anti-viral activity of melittin should be scrutinized in future studies.


Assuntos
Antivirais/farmacologia , Meliteno/farmacologia , Peptídeos/farmacologia , Vírus/efeitos dos fármacos , Animais , Camundongos , Peptídeos/química
16.
Med Chem ; 16(1): 4-23, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31203807

RESUMO

BACKGROUND: Thiazole is a good nucleus owing to its various pharmaceutical applications. Thiazole containing compounds (thiazoles) have shown various biological activities like antioxidant, analgesic, antibacterial, anticancer, antiallergic, antihypertensive, antiinflammatory, antimalarial, antifungal and antipsychotic. The scaffold is present in more than 18 FDA approved drugs and also in more than 70 experimental drugs. Only a few reviews are available in the literature despite its great medicinal importance. During the course of time, this scaffold has been studied extensively for its antiviral activities and provided compounds with activity in the nM range. However, no focused review is available on the compilation of antiviral activities shown by this scaffold. OBJECTIVE: In the present review, we have made an effort to compile antiviral literature of thiazoles reported from the year 2011 to till date. METHODS: We searched the SciFinder database (excluding patent literature) with keywords like "antiviral", "anti-HIV" and "virus". Further filters were applied for the year of publication and keywords thiazole, reviews etc. to find relevant literature reported on the antiviral activities of thiazoles. RESULTS: Nearly, 50 research articles were selected to compile and review the antiviral literature of thiazoles reported from the year 2011 to till date. Compounds 8, 25, 40, 62, 72, 73, 91, 112, 113, 131, 137, 175, 198, 200, 201 and 213 were reported in the literature with potent antiviral activity against CVB, SARS, RSV, HCV, HRV, VZV, TMV, FMDV, DENV, YFV, influenza virus, Junin virus, HIV-1, HSV, VV and EBV, respectively. CONCLUSION: There is further scope for the synthesis and evaluation of novel thiazole compounds by taking the most active compounds as lead structures. In conclusion, this review provides an overview of antiviral activities of thiazole compounds reported from the year 2011 to till date.


Assuntos
Antivirais/farmacologia , Tiazóis/farmacologia , Vírus/efeitos dos fármacos , Antivirais/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Tiazóis/química
17.
Biochem Pharmacol ; 171: 113710, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31726046

RESUMO

Enteric viruses that inhabit the intestine have profound effects on innate and adaptive immunity of the gut and thus distant organs. Acute pancreatitis (AP) is a common abdominal inflammatory disease, in which gut bacteria play an indispensable part, particularly in the severe form with local and systemic complications. So far, little is known about the role of enteric viruses in the pathophysiology of AP. In this study, we evaluated the effect of enteric virus depletion by oral anti-viral cocktail (AVC) on caerulein (Cae)-hyperstimulation induced experimental AP and underlying mechanisms. We found that AVC treatment alleviated experimental AP, accompanied by suppressed innate immune cell infiltration and TLR9 expression and signaling in pancreas and intestine. Furthermore, AVC administration reduced AP-induced interleukin-6 (IL-6) production, IL-6-activated signal transducers and activators of transcription 3 (STAT3) signaling. Concordantly, expression of AP-induced STAT3-responsive chemokines, especially monocyte chemotactic protein-1 (MCP-1) and chemokine (C-X-C motif) ligand 1 (CXCL1) was reduced, thereby contributing to modulated pancreatic immune milieu. Treatment of mice with a toll-like receptor 9 (TLR9) agonist abolished the protective effect of AVC by activation of IL6/STAT3 signaling and downstream chemokine production. Conversely, treatment of mice with TLR9 antagonists, mimicking AVC, exerted protective effects against AP. Collectively, these results suggest that depletion of enteric viruses protects mice from experimental AP through inhibiting TLR9 signaling. Our study therefore implies a previously unrecognized role of enteric viruses in AP.


Assuntos
Antivirais/farmacologia , Mucosa Intestinal/metabolismo , Pancreatite/metabolismo , Receptor Toll-Like 9/metabolismo , Vírus/efeitos dos fármacos , Animais , Ceruletídeo , Quimiocinas/metabolismo , Feminino , Interleucina-6/metabolismo , Mucosa Intestinal/virologia , Camundongos Endogâmicos BALB C , Pancreatite/induzido quimicamente , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor Toll-Like 9/agonistas , Receptor Toll-Like 9/antagonistas & inibidores , Virulência/efeitos dos fármacos , Vírus/patogenicidade
18.
Protein Pept Lett ; 27(1): 4-16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31438824

RESUMO

Antimicrobial peptides in recent years have gained increased interest among scientists, health professionals and the pharmaceutical companies owing to their therapeutic potential. These are low molecular weight proteins with broad range antimicrobial and immuno modulatory activities against infectious bacteria (Gram positive and Gram negative), viruses and fungi. Inability of micro-organisms to develop resistance against most of the antimicrobial peptide has made them as an efficient product which can greatly impact the new era of antimicrobials. In addition to this these peptides also demonstrates increased efficacy, high specificity, decreased drug interaction, low toxicity, biological diversity and direct attacking properties. Pharmaceutical industries are therefore conducting appropriate clinical trials to develop these peptides as potential therapeutic drugs. More than 60 peptide drugs have already reached the market and several hundreds of novel therapeutic peptides are in preclinical and clinical development. Rational designing can be used further to modify the chemical and physical properties of existing peptides. This mini review will discuss the sources, mechanism and recent therapeutic applications of antimicrobial peptides in treatment of infectious diseases.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias/efeitos dos fármacos , Interações Medicamentosas , Resistência Microbiana a Medicamentos , Fungos/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Peso Molecular , Resultado do Tratamento , Vírus/efeitos dos fármacos
19.
Carbohydr Polym ; 228: 115381, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31635744

RESUMO

Sargassum fusiforme polysaccharides, acidic water-soluble polysaccharides extract from Sargassum fusiforme, are mainly composed of alginic acid, fucoidan and laminaran. Alginic acid is carboxyl-containing polysaccharide formed by joining ß-D-mannuronic acid and α-L-guluronic acid through ß-(1→4)/α-(1→4) glycosidic bond. Fucoidan, a natural water-soluble sulfated heteropolysaccharide with fucose and sulfuric acid groups as the core structure, is mainly linked by L-fucose through α-(1→3) glycosidic bond and has the strongest biological activity. Laminaran is mainly composed of ß-D-glucose through ß-(1→3) glycosidic bond linkage. Sargassum fusiforme polysaccharides have a variety of pharmacological activities, including antioxidant, anti-tumor, promoting immunity, anti-aging, prompting bone growth, lowering blood glucose, anti-coagulation, anti-virus, anti-bacteria, anti-fatigue, promoting growth and development, and skin protection. These activities are closely related to the functions of fucoidan in Sargassum fusiforme polysaccharides, which fucoidan is able to strengthen immune system and antioxidation in human body. In this review, the composition, the isolation and purification, and the biological activities of Sargassum fusiforme polysaccharides are discussed and can bereference for further study.


Assuntos
Ácido Algínico , Glucanos , Polissacarídeos , Sargassum/metabolismo , Envelhecimento/efeitos dos fármacos , Ácido Algínico/química , Ácido Algínico/isolamento & purificação , Ácido Algínico/farmacologia , Animais , Bactérias/efeitos dos fármacos , Linhagem Celular , Carboidratos da Dieta/isolamento & purificação , Carboidratos da Dieta/farmacologia , Glucanos/química , Glucanos/isolamento & purificação , Glucanos/farmacologia , Humanos , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Camundongos , Neoplasias/tratamento farmacológico , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Ratos , Vírus/efeitos dos fármacos
20.
Eur J Med Chem ; 185: 111804, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675510

RESUMO

The emergence of drug resistance has created unmet medical need for the development of new classes of antibiotics. Innovation of new antibacterial agents with new mode of action remains a high priority universally. Triazines are six-membered, nitrogen-containing heterocyclic scaffold with a wide range of pharmaceutical properties such as antibacterial, antifungal, anticancer, antioxidants, antitubercular, antimalarial, anti-HIV, anticonvulsant, anti-inflammatory, antiulcer, and analgesic activities. The present review focuses on the recent developments in the area of medicinal chemistry to discover various chemical structures as potential antimicrobial agents and their structure-activity relationships (SAR) studies are also discussed for further rational design of this kind of derivatives.


Assuntos
Antibacterianos/farmacologia , Antivirais/farmacologia , Bactérias/efeitos dos fármacos , Triazinas/farmacologia , Vírus/efeitos dos fármacos , Antibacterianos/química , Antivirais/química , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Triazinas/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA