Análise energética dos fármacos Zanamivir e Oseltamivir associados a neuraminidase selvagem e com mutação HIS274TIR
Influenza A (H1N1) is an acute and contagious respiratory disease. Its strain was approved in early 2009, and was less than half the causes of pandemics in humans. The virus infection mechanism provides the medium for the two surface glycoproteins, a hemagglutinin and a neuraminidase. A hemagglut...
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H1N1 Mutação DFT MFCC Energia de interação |
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H1N1 Mutação DFT MFCC Energia de interação Souza, Mylene Radmila de Oliveira Análise energética dos fármacos Zanamivir e Oseltamivir associados a neuraminidase selvagem e com mutação HIS274TIR |
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Influenza A (H1N1) is an acute and contagious respiratory disease. Its strain was
approved in early 2009, and was less than half the causes of pandemics in humans.
The virus infection mechanism provides the medium for the two surface glycoproteins,
a hemagglutinin and a neuraminidase. A hemagglutinin binds to sialic acid receptors,
inducing the incorporation of viral envelope by the cell and an age of neuraminidase
cleaving sialic acid from cellular receptors. This mechanism prevents viral clustering
and, therefore, has become an important target for antiviral drugs. Currently,
Oseltamivir and Zanamivir are the agents of choice for the treatment and prophylaxis
of influenza because they have advantages over other drugs, however, cases of
resistance to them have already been described, which has become a reason for
concern for healthcare professionals. Cheers. Such resistance is caused by
substitutions of amino acids that are located in the neuraminidase active site, which
can influence the affinity and specificity of the binding to the receptor. The replacement
of histidine with tyrosine (His274Tir) is the most commonly found. From the
crystallographic structures of the chosen proteins (3TI6), (3CL0), (3TI5) and (3CKZ),
the interaction energy of Zanamivir and Oseltamivir co-crystallized with the wild
neuraminidase and with the His274Tir mutation was calculated using techniques
models of molecular modeling, based on the Functional Density Theory (DFT)
approach associated with the Molecular Fractionation Method with Conjugated Covers
(MFCC). The results obtained found that the residues with the most significant energy
values residues are located in the neuraminidase active site interacting with the two
angonists studied, this fact emphasizes the importance of keeping them preserved in
order not to compromise the affinity between them. With this knowledge, it is possible
to improve the design of drugs so that they can be more efficient in combating the
spread of influenza. |
| author2 |
Fulco, Umberto Laino |
| author_facet |
Fulco, Umberto Laino Souza, Mylene Radmila de Oliveira |
| format |
masterThesis |
| author |
Souza, Mylene Radmila de Oliveira |
| author_sort |
Souza, Mylene Radmila de Oliveira |
| title |
Análise energética dos fármacos Zanamivir e Oseltamivir associados a neuraminidase selvagem e com mutação HIS274TIR |
| title_short |
Análise energética dos fármacos Zanamivir e Oseltamivir associados a neuraminidase selvagem e com mutação HIS274TIR |
| title_full |
Análise energética dos fármacos Zanamivir e Oseltamivir associados a neuraminidase selvagem e com mutação HIS274TIR |
| title_fullStr |
Análise energética dos fármacos Zanamivir e Oseltamivir associados a neuraminidase selvagem e com mutação HIS274TIR |
| title_full_unstemmed |
Análise energética dos fármacos Zanamivir e Oseltamivir associados a neuraminidase selvagem e com mutação HIS274TIR |
| title_sort |
análise energética dos fármacos zanamivir e oseltamivir associados a neuraminidase selvagem e com mutação his274tir |
| publisher |
Universidade Federal do Rio Grande do Norte |
| publishDate |
2021 |
| url |
https://repositorio.ufrn.br/handle/123456789/31727 |
| work_keys_str_mv |
AT souzamyleneradmiladeoliveira analiseenergeticadosfarmacoszanamivireoseltamivirassociadosaneuraminidaseselvagemecommutacaohis274tir |
| _version_ |
1773961883264483328 |
| spelling |
ri-123456789-317272021-03-07T08:50:47Z Análise energética dos fármacos Zanamivir e Oseltamivir associados a neuraminidase selvagem e com mutação HIS274TIR Souza, Mylene Radmila de Oliveira Fulco, Umberto Laino http://lattes.cnpq.br/5858947460858441 http://lattes.cnpq.br/9579151361576173 Albuquerque, Eudenilson Lins de http://lattes.cnpq.br/3594651355252245 Bezerra, Katyanna Sales http://lattes.cnpq.br/5246433025467179 Barbosa Filho, Francisco Ferreira http://lattes.cnpq.br/2664045440231962 H1N1 Mutação DFT MFCC Energia de interação Influenza A (H1N1) is an acute and contagious respiratory disease. Its strain was approved in early 2009, and was less than half the causes of pandemics in humans. The virus infection mechanism provides the medium for the two surface glycoproteins, a hemagglutinin and a neuraminidase. A hemagglutinin binds to sialic acid receptors, inducing the incorporation of viral envelope by the cell and an age of neuraminidase cleaving sialic acid from cellular receptors. This mechanism prevents viral clustering and, therefore, has become an important target for antiviral drugs. Currently, Oseltamivir and Zanamivir are the agents of choice for the treatment and prophylaxis of influenza because they have advantages over other drugs, however, cases of resistance to them have already been described, which has become a reason for concern for healthcare professionals. Cheers. Such resistance is caused by substitutions of amino acids that are located in the neuraminidase active site, which can influence the affinity and specificity of the binding to the receptor. The replacement of histidine with tyrosine (His274Tir) is the most commonly found. From the crystallographic structures of the chosen proteins (3TI6), (3CL0), (3TI5) and (3CKZ), the interaction energy of Zanamivir and Oseltamivir co-crystallized with the wild neuraminidase and with the His274Tir mutation was calculated using techniques models of molecular modeling, based on the Functional Density Theory (DFT) approach associated with the Molecular Fractionation Method with Conjugated Covers (MFCC). The results obtained found that the residues with the most significant energy values residues are located in the neuraminidase active site interacting with the two angonists studied, this fact emphasizes the importance of keeping them preserved in order not to compromise the affinity between them. With this knowledge, it is possible to improve the design of drugs so that they can be more efficient in combating the spread of influenza. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES A influenza A (H1N1) é uma virose respiratória aguda e contagiosa. Sua cepa foi reconhecida no início do ano de 2009, e constitui pelo menos a metade das causas de pandemias de gripes em humanos. O mecanismo de infecção do vírus se dá por meio das duas glicoproteínas de superfície, a hemaglutinina e a neuraminidase. A hemaglutinina liga-se aos receptores do ácido siálico, induzindo a incorporação do envelope viral pela célula e a neuraminidase age clivando o ácido siálico dos receptores celulares. Esse mecanismo impede o agrupamento viral e, por esse motivo, tornou-se um importante alvo para fármacos antivirais. Atualmente, o Oseltamivir e o Zanamivir são os agentes de escolha para o tratamento e profilaxia da gripe por apresentar vantagens em relação aos outros fármacos, entretanto, já foram descritos casos de resistência a eles, o que se tornou motivo de preocupação para os profissionais de saúde. Tal resistência é acarretada por substituições de aminoácidos que se localizam no sítio ativo da neuraminidase, o que pode influenciar na afinidade e especificidade da ligação ao receptor. A substituição da histidina por uma tirosina (HIS274TIR) é a mais encontrada. A partir da obtenção das estruturas cristalográficas das proteínas escolhidas (3TI6), (3CL0), (3TI5) e (3CKZ) foi calculada a energia de interação do Zanamivir e Oseltamivir co-cristalizado à neuraminidase selvagem e com a mutação His274Tir, através de técnicas computacionais de modelagem molecular, com base na abordagem da Teoria Funcional da Densidade (DFT) associada ao Método de Fracionamento Molecular com Capas Conjugadas (MFCC). Os resultados obtidos constataram que os resíduos com os valores energéticos mais significativos estão situados no sítio ativo da neuraminidase interagindo com os dois antagonistas estudados, tal fato enfatiza a importância de mantê-los preservados com o objetivo de não comprometer a afinidade entre eles. Com esse conhecimento, é possível realizar um aprimoramento no design dos fármacos para que estes possam ser mais específicos e eficientes no combate à disseminação da gripe. 2021-03-05T23:38:21Z 2021-03-05T23:38:21Z 2020-09-11 masterThesis SOUZA, Mylene Radmila de Oliveira. Análise energética dos fármacos Zanamivir e Oseltamivir associados a neuraminidase selvagem e com mutação HIS274TIR. 2020. 67f. Dissertação (Mestrado em Ciências Biológicas) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2020. https://repositorio.ufrn.br/handle/123456789/31727 pt_BR Acesso Aberto application/pdf Universidade Federal do Rio Grande do Norte Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS BIOLÓGICAS |