Banca de DEFESA: GABRIELA SALVADOR OURIQUE

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : GABRIELA SALVADOR OURIQUE
DATA : 08/08/2018
HORA: 14:30
LOCAL: Anfiteatro dos Répteis
TÍTULO:

In silico study of the interaction of the NS3-NS2B protease of different flaviviruses with a peptide inhibitor

PALAVRAS-CHAVES:

Flaviviridae, Flaviviruses , West Nile Virus, NS3-NS2B, Bz-Nle-Lys-Arg-Arg-H, DFT

PÁGINAS: 128
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
RESUMO:

Flaviviridae is a large family of viral pathogens responsible for various diseases and high mortalities worldwide. Dengue (DV), Zika (ZV), West Nile Virus (WNV), Yellow Fever (YF), Hepatitis C (HC) and Japanese Encephalitis (JEV) cause important infectious diseases and are members of this family. Most of these infections does not have neither commercialized vaccines nor antiviral drugs, and their treatment are still only symptomatic. Such infections have a very similar genome. Many research groups are nowadays concentrating their efforts to find a specific inhibitory molecule for some viral proteins essential for replication.

With the advancement of sophisticated molecular modeling techniques, in conjunction with growing investigations in vivo and in vitro, we intend in this thesis to study separately the inhibition of the NS3-NS2B protease of the West Nile Virus as well as the Dengue Virus. The tetrapeptide inhibitor Bz-Nle-Lys-Arg-Arg-H, with a high inhibition constant, has been presented in the literature as a potent blockade of the NS3 protease for several Flaviviruses, besides being a smart strategy for the treatment of infections caused by this viral family. We intend to investigate the interactions of the ligand with the active site, providing a clearer and deeper insight of them. For that purpose, an in silico study was developed using quantum chemistry calculations, based on the Density Functional Theory (DFT). The interaction energy of each amino acid of the binding site with the linker was theoretically calculated by means of the Molecular Fragmentation Method with Conjugated Caps (MFCC) approach. In addition to energy, the distances, types of molecular interactions and atomic groups involved were also determined. Partial results for these Flaviviruses fever demonstrated that the inhibitor has a good affinity for the active site of the NS3-NS2B protease for both viruses, being therefore, a good candidate for an antiviral treatment specific to Flaviviruses. The work also presented the list of the most important residues for the inhibitor-receptor binding, i.e., the amino acid residues that contribute the most and least favoring this interaction.

MEMBROS DA BANCA:
Presidente - 6345638 - EUDENILSON LINS DE ALBUQUERQUE
Externo ao Programa - 2985070 - JONAS IVAN NOBRE OLIVEIRA
Externo à Instituição - JOSE ALZAMIR PEREIRA DA COSTA - UERN
Externo ao Programa - 1354851 - MANOEL SILVA DE VASCONCELOS
Interno - 1352009 - UMBERTO LAINO FULCO
Externo à Instituição - VALDER NOGUEIRA FREIRE - UFC