Busca por flavonoides como potencial ligante ao domínio RBD da proteína S para combate da Covid-19 por meio da plataforma DockThor
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Data
2022-06-15
Autores
Garcia, Camila Gonçalves
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O enfrentamento da pandemia, iniciada no ano de 2019 e ocasionada pelo novo coronavírus, o SARS-CoV-2, tem provocado muitos desafios para a ciência do mundo todo. É inédito o modo acelerado, pelo qual vem ocorrendo a busca por potenciais tratamentos de combate ao vírus. Na esteira dessa preocupação, esta pesquisa tem como objetivo buscar flavonoides com potencial de ligantes ao domínio RBD da proteína S, para o combate da Covid-19. A busca tem como objeto seis farmacológicos originados da flora brasileira. Trata-se de flavonoides, compostos com considerável capacidade de promover benefícios à saúde. A definição da estrutura do domínio RBD, da proteína Spike (S) do SARS-CoV-2, que foi utilizada nesta pesquisa, se deu a partir de uma busca em bancos de dados, por estruturas do SARS-CoV-2 com e sem inibidores complexados. A seleção dos seis flavonoides aplicados na busca por novos inibidores, junto ao SARS-CoV-2, foi realizada a partir do estudo de alguns trabalhos que pesquisaram os diferentes tipos desses compostos fenólicos. Em seguida, realizou-se o docking molecular dos compostos e estruturas selecionados na proteína alvo. Foram realizados dockings utilizando a estrutura RBD da proteína S, com o receptor ACE2 humano e sem a ACE2, permitindo a comparação entre os resultados encontrados. Essa comparação entre os dockings, com e sem a ACE2, permitiu observar por exemplo diferenças nas quantidades de aminoacidos encontrados e na qualificação posicional da genisteína. Desse modo, teve-se como resultado a determinação de um conjunto de compostos promissores, sendo possível destacar que a melhor correlação foi verificada nas áreas próximas às folhas β antiparalelas da estrutura analisada.
Facing the pandemic, which began in 2019 and caused by the new coronavirus, SARS-CoV-2, has caused many challenges for science around the world. The accelerated way in which the search for potential treatments to combat the virus has been taking place is unprecedented. In the wake of this concern, this research aims to seek flavonoids with potential as S-protein ligands to combat Covid-19. The search has as its object six pharmacological products originated from the Brazilian flora. These are flavonoids, compounds with considerable capacity to promote health benefits. The use of the Spike (S) protein of SARS CoV-2 as a target was defined from a search in databases, for structures of SARS-CoV-2 with and without complexed inhibitors. The definition of the six flavonoids used in the search for new inhibitors, together with SARS-CoV-2, was carried out from the study of some works that researched the different types of these phenolic compounds. Then, the molecular docking of the selected compounds and structures in the target protein was performed. Dockings were performed using the RBD structure of protein S, with the human ACE2 receptor and without the ACE2, allowing the comparison between the results found. This comparison between the dockings, with and without ACE2, allowed us to observe, for example, differences in the amounts of amino acids found and in the positional qualification of genistein. Thus, the result was the determination of a set of promising compounds, being possible to highlight that the best correlation was verified in the areas close to the antiparallel β sheets of the analyzed structure.
Facing the pandemic, which began in 2019 and caused by the new coronavirus, SARS-CoV-2, has caused many challenges for science around the world. The accelerated way in which the search for potential treatments to combat the virus has been taking place is unprecedented. In the wake of this concern, this research aims to seek flavonoids with potential as S-protein ligands to combat Covid-19. The search has as its object six pharmacological products originated from the Brazilian flora. These are flavonoids, compounds with considerable capacity to promote health benefits. The use of the Spike (S) protein of SARS CoV-2 as a target was defined from a search in databases, for structures of SARS-CoV-2 with and without complexed inhibitors. The definition of the six flavonoids used in the search for new inhibitors, together with SARS-CoV-2, was carried out from the study of some works that researched the different types of these phenolic compounds. Then, the molecular docking of the selected compounds and structures in the target protein was performed. Dockings were performed using the RBD structure of protein S, with the human ACE2 receptor and without the ACE2, allowing the comparison between the results found. This comparison between the dockings, with and without ACE2, allowed us to observe, for example, differences in the amounts of amino acids found and in the positional qualification of genistein. Thus, the result was the determination of a set of promising compounds, being possible to highlight that the best correlation was verified in the areas close to the antiparallel β sheets of the analyzed structure.
Descrição
Palavras-chave
Proteína S, Triagem, Docking molecular, Covid-19, DockThor, Protein S, Screening, Molecular Docking