Síntese e avaliação biológica de peptídeos contra o SARS-CoV-2
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Data
2022-05-20
Autores
Peiró, Augusto
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Universidade Estadual Paulista (Unesp)
Resumo
Pandemias como a causada pelo SARS-CoV-2 afetam todos os setores da sociedade trazendo danos difíceis de serem superados. A alta e rápida disseminação da COVID-19 promoveu a saturação de hospitais e centros de saúde, fato que contribuiu para o aumento de mortes em todo o mundo. Diante do atual quadro de pandemia e do grande problema de saúde pública mundial que o vírus SARS-CoV-2 representa, além da necessidade de desenvolvimento de tratamentos eficazes para essa doença e possíveis epidemias/pandemias futuras, é de suma importância o estudo voltado para a identificação de novos compostos com ação antiviral. O presente estudo tem por objetivo sintetizar e avaliar o potencial de dois peptídeos e um bioconjugado contra o SARS-CoV-2. Neste trabalho, estes compostos foram sintetizados, purificados e avaliados quanto a sua atividade antiviral, capacidade de inibição de protease e toxicidade em células Vero. Além disso, estudos de dicroísmo circular e permeabilização de vesículas também foram realizados. Todos os compostos mostraram tendência em estruturar em α-hélice, principalmente em TFE. Os estudos de permeabilização mostraram que os peptídeos AG-M5 e o dímero M5 possuem uma grande capacidade de interagir e permeabilizar a membrana, enquanto que o peptídeo M5 demonstrou uma baixa capacidade de permeabilização. Esses resultados estão de acordo com os dados de citotoxicidade, onde o peptídeo dímero M5 demonstrou ser bastante tóxico, sendo que o peptídeo M5 mostrou a menor citotoxicidade. Os compostos não mostraram atividade antiviral contra o SARS-CoV-2, no entanto, apresentaram atividade inibitória na enzima PLpro. Este fato, pode ser atribuído a baixa capacidade de penetração celular destes compostos. Apesar da falta de atividade antiviral, os compostos avaliados neste projeto podem colaborar no desenvolvimento de novas moléculas visando a inibição da enzima PLpro.
Pandemics as caused by SARS-Cov-2 affect all sectors of society, bringing damage that is difficult to overcome. The high and rapid spread of COVID-19 promoted the saturation of hospitals and health centers, a fact that contributed to the increase in deaths worldwide. In view of the current pandemic situation and the great global public health problem that the SARS-CoV-2 virus represents, in addition to the need to develop effective treatments for this disease and possible future epidemics/pandemics, the study aimed at the identification of new compounds with antiviral action. The present study has as its subject to synthesize and evaluate the potential of two peptides and a bioconjugate against SARS-CoV-2. In this work, these compounds were synthesized, purified and evaluated for their antiviral activity, protease inhibition capacity and toxicity in Vero cells. In addition, circular dichroism and vesicle permeabilization studies were also performed. All compounds showed a tendency to structure in α-helix, mainly in TFE. The permeabilization studies showed that the AG-M5 peptides and the M5 dimer have a great ability to interact and permeabilize the membrane, while the M5 peptide showed a low permeabilization capacity. These results are in agreement with the cytotoxicity data, where the M5 dimer peptide proved to be quite toxic, with the M5 peptide showing the lowest cytotoxicity. The compounds did not show antiviral activity against SARS-CoV-2, however they did show inhibitory activity on the PLpro enzyme. This fact can be attributed to the low cellular penetration capacity of these compounds. Despite the lack of antiviral activity, the compounds evaluated in this project can collaborate in the development of new molecules aimed at inhibiting the PLpro enzyme.
Pandemics as caused by SARS-Cov-2 affect all sectors of society, bringing damage that is difficult to overcome. The high and rapid spread of COVID-19 promoted the saturation of hospitals and health centers, a fact that contributed to the increase in deaths worldwide. In view of the current pandemic situation and the great global public health problem that the SARS-CoV-2 virus represents, in addition to the need to develop effective treatments for this disease and possible future epidemics/pandemics, the study aimed at the identification of new compounds with antiviral action. The present study has as its subject to synthesize and evaluate the potential of two peptides and a bioconjugate against SARS-CoV-2. In this work, these compounds were synthesized, purified and evaluated for their antiviral activity, protease inhibition capacity and toxicity in Vero cells. In addition, circular dichroism and vesicle permeabilization studies were also performed. All compounds showed a tendency to structure in α-helix, mainly in TFE. The permeabilization studies showed that the AG-M5 peptides and the M5 dimer have a great ability to interact and permeabilize the membrane, while the M5 peptide showed a low permeabilization capacity. These results are in agreement with the cytotoxicity data, where the M5 dimer peptide proved to be quite toxic, with the M5 peptide showing the lowest cytotoxicity. The compounds did not show antiviral activity against SARS-CoV-2, however they did show inhibitory activity on the PLpro enzyme. This fact can be attributed to the low cellular penetration capacity of these compounds. Despite the lack of antiviral activity, the compounds evaluated in this project can collaborate in the development of new molecules aimed at inhibiting the PLpro enzyme.
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Palavras-chave
Sars-cov-2, PLpro, Papain-like protease, Peptídeos, Inibidores