Banca de QUALIFICAÇÃO: MYLENE RADMILA DE OLIVEIRA SOUZA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : MYLENE RADMILA DE OLIVEIRA SOUZA
DATE: 12/08/2020
TIME: 14:00
LOCAL: online
TITLE:

ENERGY ANALYSIS OF ZANAMIVIR AND OSELTAMIVIR DRUGS ASSOCIATED WITH WILD NEURAMINIDASE AND HIS274TIR MUTATION

KEY WORDS:

H1N1, Mutation, DFT, MFCC, interaction energy

PAGES: 64
BIG AREA: Ciências Biológicas
AREA: Biofísica
SUMMARY:

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. Transmission occurs through contact with people with symptoms and symptoms characterized by fever above 39ºC, sore throat, runny nose, dry drought, headache, muscle pain and fatigue. 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 in the wild neuraminidase complex associated with oseltamivir are: Arg118; Glu119; Arg371; Asp151; Arg152; Arg292; Arg156; Glu227; His274 and Asn347; in the oseltamivir-associated mutant neuraminidase complex, the most important are: Arg118; Glu119; Arg152; Arg371; Asp151; Arg292; Tir347; Glu227 and Tir274; in the wild neuraminidase complex associated with zanamivir, the most important residues are: Arg118; Asp151; Trp178; Glu276; Arg371; Arg152; Arg156; Ser179; Arg292; Glu227; Glu277; His274; Asn347 and finally, in the mutant neuraminidase complex associated with zanamivir are: Arg118; Asp151; Arg152; Glu276; Arg371; Arg156; Trp178; Tir; 274; Arg292; Tir347; Glu227 and Glu277. According to the literature, most of these 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.

BANKING MEMBERS:
Presidente - 1352009 - UMBERTO LAINO FULCO
Externo ao Programa - 076.114.664-45 - JOSÉ XAVIER DE LIMA NETO
Externa ao Programa - 051.067.144-60 - KATYANNA SALES BEZERRA