Banca de QUALIFICAÇÃO: GABRIELA SALVADOR OURIQUE

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE : GABRIELA SALVADOR OURIQUE
DATA : 14/12/2017
HORA: 14:00
LOCAL: Sala Carl Peter von Dietrich - Departamento de Bioquímica
TÍTULO:

In silico study of the NS3-NS2B protease interaction of different flaviviruses

with a peptidic inhibitor.

PALAVRAS-CHAVES:

WNV, NS3-NS2B, Flavivirus, DFT, Inhibitor, molecular modeling

PÁGINAS: 76
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, West Nile Virus, Yellow Fever (YF), Hepatitis C (HC) and Japanese Encephalitis (JEV) cause important infectious diseases, and are also members of this family. Most of these infections do not have commercialized vaccines nor antiviral drugs, and the treatment still only symptomatic. Such infections have a very similar genome. Many research groups have been dedicated to finding a specific inhibitory molecule for some viral proteins essential for replication. With the advancement of molecular modeling techniques, in conjunction with growing work in vivo, this work aims to study separately the inhibition of the NS3-NS2B protease of West Nile Virus and Zika Virus. The Bz-Nle-Lys-Arg-Arg-H tetrapeptide inhibitor with a high inhibition constant has been reported in the literature as a potent inhibitor of the NS3 protease of various Flaviviruses. That could be a smart strategy for treating infections caused by the Flavivirus. The present work will study the interactions of the ligand with the active site to provide a clearer and deeper insight into these interactions. For that purpose, an in silico study was developed using quantum mechanics calculations, based on the Density Functional Theory (DFT). The interaction energy of each amino acid of the binding site with the linker will be calculated based on the molecular fragmentation method with conjugated caps (MFCC). In addition to energy, the distances, types of molecular interactions and atomic groups involved will be calculated. Partial results for West Nile fever demonstrated that the inhibitor has a good affinity for the active site of the NS3-NS2B protease for both viruses. Therefore, it is a good candidate for antiviral treatment specific to Flaviviruses. The work also presented the list of the most important residues for the inhibitor-receptor binding. That is, the amino acid residues that contribute the most and least favor this interaction.

MEMBROS DA BANCA:
Externo ao Programa - 1645202 - ELAINE CRISTINA GAVIOLI
Externo ao Programa - 1379465 - GILBERTO CORSO
Presidente - 2195251 - HUGO ALEXANDRE DE OLIVEIRA ROCHA