RESUMO
Persistent infections by high-risk human papillomavirus (HR-HPV) are a necessary condition, but not sufficient for cervical cancer development. Genetic variants of HR-HPV appear to be related to the risk of persistent infections. The study performed a functional evaluation of variants of the HPV-31 promoter region (LCR). For this, cloning and subcloning of variants HPV-31/UFPE-21 HPV-31/UFPE-89, HPV-31/UFPE-66, E2 gene and prototype HPV-31 were performed. Transfection with different concentrations of E2 was done and the concentration of 25 ng was determined to be ideal for LCR activation. HPV-31/UFPE-21 and HPV-31/UFPE-89 have a greater ability to alter Nluc reporter gene expression levels and HPV-31/UFPE-66 showed decreased levels of gene expression of Nluc reporter gene compared to control. Statistical analysis showed a significant difference between the polymorphic LCR regions and the control (p < 0.0001). A more refined profile of variants of HPV-31 and its importance for the prognosis of cervical lesions begins to be drawn.
Assuntos
Papillomavirus Humano 31/genética , Regiões Promotoras Genéticas , Proteínas de Ligação a DNA/metabolismo , Células HeLa , Humanos , Polimorfismo Genético , Transativadores/metabolismo , Ativação Transcricional , Proteínas Virais/metabolismoRESUMO
Coronavirus is associated with several infectious diseases that cause outbreaks in humans, such as SARS in 2002-2003 and MERS in 2012. In December 2019, COVID-19, promoted by the SARS-CoV-2 virus, was first reported in Wuhan (China) as a new coronavirus disease. This outbreak quickly reached a pandemic status, affecting at least 185 countries and territories to date on all continents. The first case of COVID-19 reported in São Paulo city (Brazil) occurred in February 26th. Days later, 182 suspected cases in 16 states were being monitored. In May 30th, 514,849 cases and 29,314 deaths were confirmed in Brazil comprising all 26 states and Federal District. The primary measure in order to contain the spread of SARS-CoV-2 involved social isolation. At that time there were not enough diagnostic tests to identify infected individuals and data were strongly associated with sub notifications. Nevertheless, the effectiveness of this measure largely depends on the individual's social responsibility. This measure has a severe economic and social impact, as in other countries. In this review, we present an overview and scientific perspectives of the evolution of COVID-19 from Brazilian databases in which climate and economic situations differ from China, European countries, and the USA.
Assuntos
Infecções por Coronavirus/epidemiologia , Serviços de Saúde/provisão & distribuição , Pneumonia Viral/epidemiologia , Betacoronavirus , Brasil/epidemiologia , COVID-19 , Humanos , Pandemias , SARS-CoV-2RESUMO
A codon-optimized equine infectious anemia virus p26 gene was fused to a maltose-binding protein (MBP) and expressed in Escherichia coli for use as an antigen in agar gel immunodiffusion (AGID) and enzyme-linked immunosorbent assay (ELISA) for diagnosis of equine infectious anemia. An analysis of analytical sensitivity and specificity showed that the antigen MBP-p26rec reacted positively with a reference World Organization for Animal Health serum and demonstrated no cross-reaction against sera from vaccinated animals in either test. The diagnostic characteristics were evaluated and presented excellent values. The AGIDrec showed 100% sensitivity and specificity, and the ELISArec showed 100% sensitivity and 99.64% specificity. In addition, MBP-p26rec was stabile after three years of storage at 4 °C, maintaining its immunoreactivity.
Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Anemia Infecciosa Equina/virologia , Imunodifusão/métodos , Vírus da Anemia Infecciosa Equina/isolamento & purificação , Proteínas Ligantes de Maltose/análise , Proteínas do Core Viral/análise , Animais , Ensaio de Imunoadsorção Enzimática/instrumentação , Anemia Infecciosa Equina/diagnóstico , Anemia Infecciosa Equina/imunologia , Cavalos , Imunodifusão/instrumentação , Vírus da Anemia Infecciosa Equina/genética , Vírus da Anemia Infecciosa Equina/imunologia , Proteínas Ligantes de Maltose/genética , Proteínas Ligantes de Maltose/imunologia , Proteínas do Core Viral/genética , Proteínas do Core Viral/imunologiaRESUMO
The classical swine fever (CSF) is a highly contagious viral disease of pigs and wild boar. The CSF causes great economic losses for pork production and the occurrence of the disease is notifiable to the OIE. The objective of this work was to identify and characterize CSF virus isolates from Brazil. Seven viral isolates were obtained and the full-length E2 sequences were analyzed. Phylogenetic analysis revealed a different segregation pattern between Brazilian isolates and members of subgenotype 1.1, forming a separate group within genotype 1. Genetic distance analysis suggested the existence of two new subgenotypes, designated subgenotypes 1.5 and 1.6.
Assuntos
Vírus da Febre Suína Clássica/genética , Vírus da Febre Suína Clássica/isolamento & purificação , Peste Suína Clássica/virologia , Animais , Animais Domésticos/virologia , Brasil , Vírus da Febre Suína Clássica/classificação , Genótipo , Filogenia , Sus scrofa/virologia , Suínos , Proteínas Virais/genéticaRESUMO
Prostate cancer is the second most common cancer among men in western populations, and despite its high mortality, its etiology remains unknown. Inflammatory processes are related to the etiology of various types of tumors, and prostate inflammation, in particular, has been associated with prostate cancer carcinogenesis and progression. Human papillomavirus (HPV) is associated with benign and malignant lesions in the anogenital tract of both females and males. The possible role of HPV in prostate carcinogenesis is a subject of great controversy. In this study, we aimed to examine the prevalence of HPV infections in prostate carcinomas of patients from northeastern Brazil. This study included 104 tissue samples from primary prostate carcinoma cases. HPV DNA was purified and then amplified using MY09/11 and GP5+/GP6+ degenerate primer sets that detect a wide range of HPV types, and with specific PCR primers sets for E6 and E7 HPV regions to detect HPV 16. None of the samples showed amplification products of HPV DNA for primer sets MY09/11 and GP5+/GP6+, or the specific primer set for the E6 and E7 HPV regions. HPV infection, thus, does not seem to be one of the causes of prostate cancer in the population studied.
RESUMO
This study reports an alternative method for black liquor treatment with potential for energy and process savings in the paper and pulp industry. Gasification of black liquor was carried out under sub- and supercritical conditions, varying the black liquor feed composition (0.10, 2.55 and 5.00 wb%) and temperature (350, 425 and 500 °C). Liquid products were identified by high resolution mass spectrometry (FT-Orbitrap MS) and compounds belonging to classes O3 and O4 were found to be the most representative in the products of reactions performed at 500 °C. The mass spectra results also revealed the overall selectivity of reactions, where decarboxylation and demethoxylation reactions were favored under subcritical and supercritical conditions, respectively. Among the gaseous products, hydrogen and methane were produced with maximum of 69.04 and 28.75 mol%, respectively, at 2.55 wb% and 425 °C. The proposed thermodynamic modelling of the reaction system satisfactorily predicted the gas phase behavior of the system. In the economic analysis, the simulated conditions indicated that the main energy requirements for a scaled-up black liquor gasification process are related to the necessary heat exchangers and pressurizing of the black liquor solution. Furthermore, the cost of the black liquor gasification is around 0.06 US$ per kg of feed stream. Liquid and gaseous products from gasification could be obtained at a cost of 56.64 US$ and 3.35 US$ per tonne of stream, respectively. Therefore, black liquor gasification is an interesting route for obtaining combustible gases and value-added bioproducts.
Assuntos
Gases , Metano , Hidrogênio , Temperatura , Termodinâmica , ÁguaRESUMO
OBJECTIVE: We sought to characterize E6 and E7 oncogenes genetic variability of HPV-31 isolated from cervical scraping samples of Northeastern Brazilian women. METHODS: E6 and E7 were amplified with specific primers, cloned and sequenced. The sequences obtained were aligned with the GenBank reference sequences with the aim of evaluating the possible genetic variants. RESULTS: We identified several genetic variants in E6 and E7 sequences from HPV-31 positive women. Three nucleotide changes in E6 were described for the first time in this study. Some nucleotide changes were non-synonymous substitutions. CONCLUSION: The knowledge of region/country HPV specific genetic variations is relevant to understand the epidemiology and the development of effective vaccines.
Assuntos
Papillomavirus Humano 31/genética , Proteínas Oncogênicas Virais/genética , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Epitopos de Linfócito B , Epitopos de Linfócito T , Feminino , Variação Genética , Humanos , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/imunologia , FilogeniaRESUMO
The severe consequences of ZIKV infection and its emergence and re-emergence in several countries have boosted vaccines' development. Yeasts such as Pichia pastoris has been widely employed as antigen carriers for immunization against infectious agents. Components of the yeast cell wall have immunostimulatory properties, and recombinant antigens can be anchored to the cell surface to enhance the presentation to the immune system. Here we aimed at producing and anchoring ZIKV proteins in the P. pastoris surface as a vaccine approach. Expression cassettes were designed with epitopes of the Envelope and NS1 proteins. Immunofluorescence microscopy confirmed the anchoring of recombinant proteins. Yeasts' ability to stimulate immune cells was evaluated in vitro by incubation with lymphocytes and monocytes isolated from mouse spleen. P. pastoris expressing EnvNS1 epitopes promoted increased levels of IL-6, IL-10, and TNF-α cytokines and an increase in the number of CD4+, CD8+, and CD16+ lymphocytes, similarly to ZIKV. This profile is indicative of the activation of immunological cells and suggests an immunogenic potential of the proposed yeast vaccines against ZIKV, reinforcing the possibility of P. pastoris as adjuvant and carrier of antigens.
Assuntos
Infecção por Zika virus , Zika virus , Animais , Epitopos , Camundongos , Pichia/genética , Proteínas Recombinantes/genética , SaccharomycetalesRESUMO
The major control methods for Aujeszky's Disease (AD) involve SHV1 gE gene-deleted vaccines and ELISA for detection of specific gE antibodies in infected animals, distinguishing infected animals from vaccinated animals (DIVA). This work aimed to develop a DIVA ELISA recombinant gE (gErec) for AD diagnosis using recombinant gE fused to thioredoxin protein. The analytical sensitivity and specificity were assessed with World Organisation for Animal Health (OIE) AD serum and sera from specific pathogen free (SPF), vaccinated SPF and AD-vaccinated SPF animals. The OIE serum reacted up to the recommended limit of detection and the other sera presented negative results. The cut-off point, diagnostic sensitivity and diagnostic specificity were determined by receiver operating curve analysis. This cut-off value corresponded to a diagnostic sensitivity of 97.60% and diagnostic specificity of 96.42%. Furthermore, two other cut-off points were chosen to discuss the ELISAgErec as a screening test in AD-endemic and free areas.
Assuntos
Anticorpos Antivirais/isolamento & purificação , Antígenos Virais/química , Ensaio de Imunoadsorção Enzimática/veterinária , Herpesvirus Suídeo 1/imunologia , Pseudorraiva/diagnóstico , Doenças dos Suínos/diagnóstico , Vacinação/veterinária , Animais , Ensaio de Imunoadsorção Enzimática/métodos , Proteínas Recombinantes/química , Sensibilidade e Especificidade , Suínos , Tiorredoxinas/químicaRESUMO
Persistent infections caused by high-risk human papillomavirus (HR-HPV) are important, for the development of cervical lesions, but environmental and genetic factors are also related in the process of carcinogenesis. Among the genetic factors, the genetic variants of HR-HPV appear to be related to the risk of persistent infections. Therefore, the present study investigates variants of HPV31 E5 oncogene in cervical scraping samples from Brazilian women to assess their functional and structural effects, in order to identify possible repercussions of these variants on the infectious and carcinogenic process. Our results detected nucleotide changes previously described in the HPV31 E5 oncogene, which may play a critical role in the development of cancer due to its ability to promote cell proliferation and signal transmission. In our study, the interaction percentage of the 31E5 sequence generated by the Immune Epitope Server database and the Analysis Resource (IEDB) allowed us to include possible immunogenic epitopes with the MHC-I and MHC-II molecules, which may represent a possible relationship between protein suppression of the immune system. In the structural analysis of the HPV31 E5 oncoprotein, the N5D, I48 V, P56A, F80I and V64I polymorphisms can be found inserted within transmembrane regions. The P56A mutation has been predicted to be highly stabilizing and, therefore, can cause a change in protein function. Regarding the interaction of the E5 protein from HPV31 with the signaling of NF-kB pathway, we observed that in all variants of the E5 gene from HPV-31, the activity of the NF-kB pathway was increased compared to the prototype. Our study contributes to a more refined design of studies with the E5 gene from HPV31 and provides important data for a better understanding of how variants can be distinguished under their clinical consequences.
Assuntos
Colo do Útero/virologia , Variação Genética , Papillomavirus Humano 31/classificação , Papillomavirus Humano 31/genética , Proteínas Oncogênicas Virais/química , Proteínas Oncogênicas Virais/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células , Feminino , Células HEK293 , Humanos , Pessoa de Meia-Idade , Mutação , Proteínas Oncogênicas Virais/classificação , Infecções por Papillomavirus/virologia , Filogenia , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Quinase Induzida por NF-kappaBRESUMO
Chagas disease (American trypanosomiasis) is one of the most important parasitic diseases with serious social and economic impacts mainly on Latin America. This work reports the synthesis, in vitro trypanocidal evaluation, cytotoxicity assays, and molecular modeling and SAR/QSAR studies of a new series of N-phenylpyrazole benzylidene-carbohydrazides. The results pointed 6k (X=H, Y=p-NO2, pIC(50)=4.55 M) and 6l (X=F, Y=p-CN, pIC(50)=4.27 M) as the most potent derivatives compared to crystal violet (pIC(50)=3.77 M). The halogen-benzylidene-carbohydrazide presented the lowest potency whereas 6l showed the most promising profile with low toxicity (0% of cell death). The best equation from the 4D-QSAR analysis (Model 1) was able to explain 85% of the activity variability. The QSAR graphical representation revealed that bulky X-substituents decreased the potency whereas hydrophobic and hydrogen bond acceptor Y-substituents increased it.
Assuntos
Antiprotozoários/síntese química , Compostos de Benzilideno/síntese química , Doença de Chagas/tratamento farmacológico , Hidrazinas/síntese química , Relação Quantitativa Estrutura-Atividade , Animais , Compostos de Benzilideno/farmacologia , Morte Celular/efeitos dos fármacos , Hidrazinas/farmacologia , Modelos Moleculares , Trypanosoma cruzi/efeitos dos fármacosRESUMO
1H-pyrazole-4-carbohydrazides were synthesized and their leishmanicidal in vitro activities and cytotoxic effects were investigated. The drugs prototypes of these new compounds (ketoconazole, benznidazole, allopurinol and pentamidine) were also tested. It was found that among all the 1H-pyrazole-4-carbohydrazides derivatives examined, the most active compounds were those with X = Br, Y = NO2 (27) and X = NO2, Y = Cl (15) derivatives which showed to be most effective on promastigotes forms of L. amazonensis than on L. chagasi and L. braziliensis species. When tested against murine peritoneal macrophages as mammalian host cell controls of toxicity, 1-(4-Br-phenyl)-N'-[(4-NO(2)-phenyl)methylene]-1H-pyrazole-4-carbohydrazides (27) (EC50 = 50 microM l(-1)) and 1-(4-NO2-phenyl)-N'-[(4-Cl-phenyl)methylene]-1H-pyrazole-4-carbohydrazides (15) EC50 = 80 microM l(-1))] was reasonably toxic. However, both compounds were less toxic than pentamidine and ketoconazole. These results provide new perspectives on the development of drugs with activities against Leishmania parasite.
Assuntos
Antiprotozoários/síntese química , Hidrazinas/síntese química , Leishmania/efeitos dos fármacos , Pirazóis/síntese química , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Hidrazinas/química , Hidrazinas/farmacologia , Leishmania/crescimento & desenvolvimento , Leishmaniose/tratamento farmacológico , Macrófagos Peritoneais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Testes de Sensibilidade Parasitária , Pirazóis/química , Pirazóis/farmacologia , Relação Estrutura-AtividadeRESUMO
Retroviral vectors are commonly used in ex vivo gene therapy protocols. The structure of vectors basically consists of one gene of interest and a selectable marker gene. Fast selection without damaging cells is a critical step for ex vivo gene therapy protocols. Blasticidin S deaminase isolated from Bacillus cereus has a neutralizing action on the highly toxic antibiotic blasticidin S (BS). A commercially available gene coding for blasticidin S deaminase (bsr) when used to construct retroviral vectors, LBSN and LNSB, provided very low levels of BS deaminase activity, precluding their routine use in gene transfer experiments. However, with the introduction of specific mutations into the bsr gene based on the Kozak consensus sequences and deletion of a 5' untranslated sequence to generate bsrm, we were able to construct a retroviral vector encoding resistance to high doses of BS (at least 16-fold above the usual lethal dose in NIH3T3 cells), showing that bsrm/BS may provide a useful system for selection of transduced mammalian cells.
Assuntos
Aminoidrolases/genética , Farmacorresistência Viral/genética , Marcadores Genéticos/genética , Vetores Genéticos/genética , Nucleosídeos/farmacologia , Retroviridae/genética , Transdução Genética/métodos , Células 3T3 , Animais , Terapia Genética/métodos , Camundongos , Vírus da Leucemia Murina de Moloney/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Seleção GenéticaRESUMO
BACKGROUND: The MDM2 gene is the major negative regulator of p53, a tumor suppressor protein. Single nucleotide polymorphism in promoter region of MDM2 gene leads to increased expression resulting in higher levels of MDM2 protein. This event increases the attenuation of the p53 pathway. Polymorphisms in this gene can interfere in the regulation of cellular proliferation. We evaluated whether MDM2 SNP309 (rs2278744) associated or not with the use of oral contraceptive can heighten susceptibility to development of cervical lesions in women HPV infected. METHODS: MDM2 SNP309 (rs2278744) was genotyped in a total of 287 patients using the PCR-RFLP technique. The results were analyzed by UNPHASED v.3.121 and SNPStats programs. RESULTS: The three groups (SIL, LSIL and HSIL) showed no significant differences in either genotype or allelic frequencies for MDM2 polymorphisms, except when HSIL was compared with LSIL (p = 0.037; OR = 1.81). Furthermore, in the analysis of contraceptives, a significant association was found between the use of contraceptives and the MDM2 variant in the development of high-grade cervical lesions for the TG genotype (p = 0.019; OR = 2.21) when HSIL was compared with control. When HSIL was compared with LSIL (p = 0.006; OR = 2.27). CONCLUSION: The results of this study suggest that MDM2 SNP309 might be a good marker for assessing the progression of LSIL to HSIL. In addition, they also show that oral contraceptives alone, did not have any effect on the progression or development of cervical lesions. However, they may act synergistically with MDM2 SNP309 (rs2278744) and HPV infection in the development of cervical lesions.
RESUMO
Porcine circovirus type 2 (PCV2) is associated with postweaning multisystemic wasting syndrome (PMWS). The PCV2 capsid (Cap) protein is a leading antigen candidate for vaccine and serological diagnostic testing, due to its immunogenic properties. In this study, the codon-optimized PCV2 Cap gene was cloned into a pPICZαA vector for secretory expression in the methylotrophic yeast Pichia pastoris after methanol induction. The screening of recombinant yeasts was followed by detection of the recombinant Cap (rCap) protein by Western blot, using sera from pigs naturally infected with PCV2. The rCap secreted protein was used without prior purification as a coating antigen in the ELISA test, with high discrimination between PCV2-positive and negative sera. These results reveal a high confidence in the specific immunoreactivity of the secreted antigen and show the antigenicity of the recombinant protein. The feasibility of the P. pastoris expression system for the production of PCV2 Cap as secreted protein and its apparent bioactivity, suggests there are good prospects for the use of this antigen in the investigation of PCV2 infections and testing for vaccine purposes.
Assuntos
Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Circovirus/genética , Pichia/genética , Animais , Anticorpos Antivirais/sangue , Antígenos Virais/genética , Western Blotting , Clonagem Molecular , DNA Viral/química , DNA Viral/genética , Ensaio de Imunoadsorção Enzimática , Expressão Gênica , Vetores Genéticos , Dados de Sequência Molecular , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomycetales , Análise de Sequência de DNA , SuínosRESUMO
Bovine papillomaviruses (BPVs) can infect epithelial cells and fibroblasts, inducing fibropapillomas in cattle. Gap junctions are communication channels between cells composed of connexins (Cxs). This study evaluated expression of Cx26 and the major BPV oncoprotein E5 in bovine cutaneous fibropapillomas. BPV DNA was amplified from 20/20 fibropapillomas and 3/3 samples of normal skin. All fibropapillomas (20/20) were positive by immunostaining for E5, whereas the three normal skin samples were negative. Cx26 was expressed faintly in the normal skin epithelium. Positive cytoplasmic and juxtanuclear immunoreactivity for Cx26 was evident in 18/20 (90%) fibropapillomas. Western blot analysis demonstrated higher expression of Cx26 in 6/6 fibropapillomas compared to normal skin samples.
Assuntos
Doenças dos Bovinos/metabolismo , Conexinas/metabolismo , Deltapapillomavirus/classificação , Infecções por Papillomavirus/veterinária , Animais , Bovinos , Doenças dos Bovinos/virologia , Conexina 26 , Feminino , Regulação da Expressão Gênica , Reação em Cadeia da PolimeraseRESUMO
Bovine papillomaviruses (BPVs) are a diverse group of double-stranded DNA viruses, of which 12 viral types have been detected and characterized so far. However, there is still a limited understanding of the diversity of BPV. Several putative new BPVs have been detected and some of these have been recently characterized as new viral types. However, only a very limited amount of information is available on the pathology associated with these novel viral types yet this information could be of significant value in improving our understanding of the biology of BPV. The objective of this study was to examine some of the epidemiological features of cutaneous bovine papillomatosis in Brazilian cattle, in particular to establish the relationship between BPV types isolated from beef and dairy cattle herds and the lesions they cause. Seventy-two cutaneous lesions were collected from 60 animals. Histopathological, PCR and sequencing assays were conducted to characterize the lesions and detect the BPV types responsible. Phylogenetic analysis was carried out using the maximum likelihood method. BPV types 1-6 and 8-10 were found, as well as a putative new BPV type that belongs to the Deltapapillomavirus genus. The tumors were all classified as fibropapillomas. This is believed to be the first record of BPV types 3 and 10 associated with fibropapillomas. These results confirm that there is a wide range of BPV types that infect cattle, and that an understanding of this diversity is necessary for improved methods of therapeutic treatment.
Assuntos
Doenças dos Bovinos/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/veterinária , Animais , Brasil/epidemiologia , Bovinos , Doenças dos Bovinos/epidemiologia , Feminino , Masculino , Epidemiologia Molecular , Papillomaviridae/classificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , FilogeniaRESUMO
The papillomaviruses form a highly diverse group that infect mammals, birds and reptiles. We know little about their genetic diversity and therefore the evolutionary mechanisms that drive the diversity of these viruses. Genomic sequences of papillomaviruses are highly divergent and so it is important to develop methods that select the most phylogenetic informative sites. This study aimed at making use of a novel approach based on entropy to select suitable genomic regions from which to infer the phylogeny of papillomavirus. Comparative genomic analyzes were performed to assess the genetic variability of each gene of Papillomaviridae family members. Regions with low entropy were selected to reconstruct papillomavirus phylogenetic trees based on four different methods. This methodology allowed us to identify regions that are conserved among papillomaviruses that infect different hosts. This is important because, despite the huge variation among all papillomaviruses genomes, we were able to find regions that are clearly shared among them, presenting low complexity levels of information from which phylogenetic predictions can be made. This approach allowed us to obtain robust topologies from relatively small datasets. The results indicate that the entropy approach can successfully select regions of the genome that are good markers from which to infer phylogenetic relationships, using less computational time, making the estimation of large phylogenies more accessible.
Assuntos
Entropia , Genômica/métodos , Papillomaviridae/classificação , Papillomaviridae/genética , Animais , Sequência de Bases , Evolução Biológica , Bases de Dados Genéticas , Variação Genética , Genoma , Dados de Sequência Molecular , Fases de Leitura Aberta , Filogenia , Alinhamento de Sequência , Análise de Sequência de DNA , Proteínas Virais/química , Proteínas Virais/genéticaRESUMO
The development of new drugs against Trypanosoma cruzi is still required since the only two drugs currently used cause severe side effects. In this work we described the synthesis, the in vitro biological evaluation, and the SAR results of 1H-pyrazolo[3,4-b]pyridine derivatives, a new antichagasic agent series. The presence of fluorine, hydroxyl or nitro group at Y position resulted in at least one or two promising compounds in each set of derivatives (6f, 6g, 6i, 6l, and 6m). The SAR study showed that trypanocidal activity observed depends on both geometric and stereoelectronic parameters (MEP and frontier molecular orbitals HOMO and LUMO). We also used the Osiris program for calculating and comparing the fragment based druglikeness of the most active derivative (6g) (IC(50)=1.9microg/mL), the inactive compound (6o), and the current toxic antichagasic drugs (nifurtimox and benznidazole). Interestingly 6g presented a potential druglikeness higher than nifurtimox and benznidazole while 6o presented the lowest value among them.