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Chemical and structural aspects of Ebolavirus sp. cell entry inhibitors
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O vírus Ébola esteve na origem do surto ocorrido em 2014 resultando numa epidemia de proporções históricas na África ocidental. Constituem uma família de vírus denominada Filoviridae que inclui cinco estirpes virais e são responsáveis por infeções cujo sintoma principal são febres hemorrágicas graves. Nesta família de vírus está inserido o Ebolavirus sp.,agente causal da epidemia em questão, associado a taxas de mortalidade até 90%, tendo se tornado assim num grande foco de atenção por parte das autoridades de Saúde tais como o Instituto Nacional de Alergia e Doenças Infecciosas dos Estados Unidos da América, que devido aos sucessivos surtos de Ébola e ao consequente aumento do número de infetados e de mortos, levou à classificação do vírus como um agente de potencial ameaça biológica de categoria A. Deste modo, vários esforços foram feitos no sentido de desenvolver uma opção terapêutica viável e uma das abordagens mais apelativas para cumprir este objetivo passa pela inibição do processo viral de penetração celular. Esta opção é extremamente vantajosa considerando que bloqueia a infeção numa fase precoce diminuindo drasticamente a probabilidade da ocorrência de sintomas e aumentando a taxa de sobrevivência. O processo de penetração da célula por parte do vírus Ébola requer fusão com a célula hospedeira e a glicoproteína do invólucro viral desempenha um papel importante no decorrer desta interação. Neste trabalho procede-se à compilação da informação disponível acerca das propriedades químicas e estruturais dos inibidores do processo viral de penetração celular, entre os quais se encontram anticorpos monoclonais (MAb), péptidos-C, e pequenas moléculas.
A infeção pelo vírus Ébola é um processo complexo cujos mecanismos encontram-se ainda por elucidar, no entanto a informação aqui apresentada revela uma base promissora para a realização de mais estudos com o intuito de esclarecer estes mecanismos e desenvolver um fármaco antiviral eficaz para o tratamento da infeção pelo vírus Ébola.
The Ebola virus was the origin of a major outbreak in 2014 that caused an epidemic of historic proportions in West Africa. These viruses are a part of the Filoviridae family which symptoms include severe haemorrhagic fever. Five species are included in this family and the Ebolavirus species (EBOV) was the causative agent of the referred epidemic. It is associated with mortality rates as high as 90%, hence being the main focus of global health care authorities since the outbreak. The recurrent outbreaks have caused more concern which lead to the classification of EBOV as a category A potential biological threat agent by the National Institute of Allergy and Infectious Diseases. Consequently, there has been a concerted effort towards the development of an effective therapeutic drug. Cell entry inhibition has been a popular approach since it blocks infection at a very early step decreasing the chances symptomatic onset and increases odds for survival. EBOV cell entry requires budding and fusion with the host cell membrane, a process that involves the envelope glycoprotein (GP) and its respective interactions. On this essay we review the information available regarding the structural and chemical properties of cell entry inhibitors, among which feature monoclonal antibodies (MAb), C-peptides and small molecules. Much remains to be elucidated about EBOV’s mechanism of infection although the information reviewed herein reveals a promising foundation to be built on through further studies in order to clarify EBOV mechanism and to develop an effective antiviral drug.
The Ebola virus was the origin of a major outbreak in 2014 that caused an epidemic of historic proportions in West Africa. These viruses are a part of the Filoviridae family which symptoms include severe haemorrhagic fever. Five species are included in this family and the Ebolavirus species (EBOV) was the causative agent of the referred epidemic. It is associated with mortality rates as high as 90%, hence being the main focus of global health care authorities since the outbreak. The recurrent outbreaks have caused more concern which lead to the classification of EBOV as a category A potential biological threat agent by the National Institute of Allergy and Infectious Diseases. Consequently, there has been a concerted effort towards the development of an effective therapeutic drug. Cell entry inhibition has been a popular approach since it blocks infection at a very early step decreasing the chances symptomatic onset and increases odds for survival. EBOV cell entry requires budding and fusion with the host cell membrane, a process that involves the envelope glycoprotein (GP) and its respective interactions. On this essay we review the information available regarding the structural and chemical properties of cell entry inhibitors, among which feature monoclonal antibodies (MAb), C-peptides and small molecules. Much remains to be elucidated about EBOV’s mechanism of infection although the information reviewed herein reveals a promising foundation to be built on through further studies in order to clarify EBOV mechanism and to develop an effective antiviral drug.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2016
Palavras-chave
Haemorrhagic fever Ebola Virus Cell entry inhibition Envelope glycoprotein Mestrado Integrado - 2016