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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| Formato: | Dissertação |
| Idioma: | pt_BR |
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Universidade Federal do Rio Grande do Norte
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| Endereço do item: | https://repositorio.ufrn.br/handle/123456789/31727 |
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| Resumo: | 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. |
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