| spelling |
Edel Figueiredo Barbosa Stanciolihttp://lattes.cnpq.br/6598548690635635https://lattes.cnpq.br/5142909130780410Mateus Vitorino Guimaraes2023-08-16T15:25:40Z2023-08-16T15:25:40Z2020-02-02http://hdl.handle.net/1843/57841Os vírus encontram-se entre as principais causas de adoecimento no mundo, destacando-se o Dengue virus (DENV) que infecta anualmente cerca de 390 milhões de pessoas, das quais 96 milhões desenvolvem sintomas aparentes. Estima-se que 40% da população mundial encontra-se em áreas de risco para dengue. A dispersão da doença tem aumentado durante os últimos anos e atualmente o vírus encontra-se presente em 128 países. No Brasil, graves epidemias ocorreram nos últimos anos, causando um grande impacto econômico para o país e desfechos importantes nos indivíduos acometidos. Atualmente, não existe tratamento específico e eficaz para as infecções causadas pelo Dengue virus, sendo o cuidado médico essencial para um melhor desfecho da infecção. A busca por antivirais específicos é estratégica. Neste contexto, devido às suas propriedades farmacológicas únicas, os derivados do Adamantano aparecem como uma possibilidade, tendo demonstrado atividade antiviral comprovada para os vírus Influenza A, Human immunodeficiency virus 1 e Hepatitis C virus. Sendo assim, o objetivo do presente trabalho foi determinar in vitro a eficácia de três compostos inéditos (ADA1, ADA2 e ADA5) derivados da Amantadina, que consiste em um grupamento funcional de NH2 no carbono 5 do adamantano, contra o Dengue virus 4 (DENV-4). Os ensaios in vitro realizados com as técnicas de MTT e AlamarBlue demonstraram que os três compostos não apresentaram citotoxicidade em células BHK-21 para as concentrações de 200 μM (com exceção de ADA5), até 0.0002 μM. Os ensaios de atividade antiviral, realizados com o ensaio de redução de placas em células BHK-21, demonstraram que os compostos ADA1 e ADA2, na concentração de 200μM, reduziram em 4 (100%) e 2 log (50%), respectivamente, os títulos virais de DENV-4. Foi observada também uma redução de cerca de 1 log (25%) no título viral de DENV-4 para os três compostos nas concentrações de 20 μM e 2 μM. Em conclusão, os compostos ADA1 e ADA2 na concentração de 200 μM apresentam potencial antiviral para o modelo estudado, DENV-4, e de acordo com os resultados preliminares esta atividade extende-se aos sorotipos DENV-1, 2 e 3.Viruses are among the leading causes of illness around the world, including Dengue virus (DENV), which infects approximately 390 million people every year, of which 96 million develop apparent symptoms and it is estimated that 40% of the world population are living in areas at risk of contracting Dengue. Its dispersion has increased over the last few years, and the virus is now present in 128 countries. In Brazil serious epidemics have occurred in recent years, causing a great economic impact to the country and important outcomes in the affected individuals. Currently there is no specific and effective treatment for infections caused by Dengue virus, and medical care is essential for a better outcome of the infection. The search for specific antivirals is strategic. Due to their unique pharmacological properties, adamantane derivatives demonstrate proven antiviral activity for Influenza A, Human immunodeficiency virus 1 and Hepatitis C virus. Therefore, the aim of the present study is to determine in vitro the effectiveness of three new compounds (ADA1, ADA2 and ADA5) derived from Amantadine, which consists of a functional group of NH2 on carbon 5 of adamantane, against Dengue virus 4 (DENV-4). The assays performed with MTT and AlamarBlue techniques demonstrated that the three compounds did not show cytotoxicity in BHK-21 cells at concentrations of 200 μM (with the exception of ADA5) up to 0.0002 μM. The antiviral activity assay carried out by titration in BHK-21 cells (plaque reduction assay), demonstrated that the compounds ADA1 and ADA2, at a concentration of 200μM, reduced by 4 (100%) and 2 log (50%), respectively, the titers of DENV-4. A reduction of about 1 log (25%) in the viral titer of DENV-4 was also observed for the three compounds at concentrations of 20 μM and 2 μM. In conclusion, the compounds ADA1 and ADA2 at a concentration of 200 μM present antiviral potential for DENV-4 and according to preliminary results this potential extends to the other serotypes DENV-1, 2 and 3.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em MicrobiologiaUFMGBrasilhttp://creativecommons.org/licenses/by/3.0/pt/info:eu-repo/semantics/openAccessMicrobiologiaVírus da DengueAntiviraisAmantadinaAdamantanoDengue virusAntiviralAmantadinaAdamantanoAvaliação do potencial antiviral de compostos derivados do adamantano para dengue virusinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8914https://repositorio.ufmg.br/bitstream/1843/57841/2/license_rdff9944a358a0c32770bd9bed185bb5395MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82118https://repositorio.ufmg.br/bitstream/1843/57841/3/license.txtcda590c95a0b51b4d15f60c9642ca272MD53ORIGINALDissertação_Mateus Vitorino Guimarães_Versão corrigida.pdfDissertação_Mateus Vitorino Guimarães_Versão corrigida.pdfapplication/pdf2583349https://repositorio.ufmg.br/bitstream/1843/57841/4/Disserta%c3%a7%c3%a3o_Mateus%20Vitorino%20Guimar%c3%a3es_Vers%c3%a3o%20corrigida.pdfe4444fa11d9e7017ae2316e048ab109bMD541843/578412023-10-23 13:39:43.168oai:repositorio.ufmg.br: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ório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-10-23T16:39:43Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
|