Banca de DEFESA: LARISSA CELESTINO DA SILVA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : LARISSA CELESTINO DA SILVA
DATE: 18/04/2026
TIME: 09:00
LOCAL: Videoconferência
TITLE:

EXPLORING POTENTIAL INHIBITORS FOR THE CHIKUNGUNYA VIRUS NSP3 MACRODOMAIN

KEY WORDS:

Chikungunya Virus, Macrodomain (nsP3MD), Molecular Modeling, DFT, MFCC.

PAGES: 77
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Arboviruses represent a growing public health problem, among which Chikungunya fever (CHIKF) stands out. This viral disease is transmitted mainly by Aedes aegypti and Aedes albopictus mosquitoes and is characterized by acute fever and intense arthralgia that can evolve into chronic joint manifestations. The lack of widely available vaccines or specific antivirals makes the infection a significant challenge for global public health. Among the central factors in viral replication is the non-structural protein 3 (nsP3), whose macrodomain (nsP3MD) plays an essential role in the hydrolysis of ADP-ribose and in evading the host's immune response, making it a promising target for drug development. In this work, we investigated three pyrimidone-derived compounds — 2-oxo-1,2-dihydroquinazoline-4-carboxylic acid (SRI-43750), 2-oxo-1,2,5,6,7,8-hexahydroquinazoline-4-carboxylic acid (SRI-43945), and methyl 2-oxo-1,2-dihydroquinazoline-4-carboxylate (SRI-44019) — in complex with nsP3MD, seeking to elucidate their molecular interactions and inhibitory potential against this protein. To this end, we used crystallographic structures available in the PDB and applied advanced computational methods from the perspective of Molecular Modeling through the Molecular Fractionation with Conjugated Caps (MFCC) method, in accordance with the calculation conditions established by Density Functional Theory (DFT). The analyses were conducted considering a radius of up to 10.0 Å around the inhibitors. The results revealed that the ligands stabilize at the ADP-ribose binding site through hydrogen bonds, hydrophobic interactions, and π-π stacking with key residues such as TYR114, GLY112, and VAL113. Among the compounds evaluated, SRI-43750 showed the most expressive interactions, followed by SRI-43945 and SRI-44019. These findings provide relevant evidence for the rational design of new antivirals targeting the nsP3 macrodomain, offering prospects for innovative therapies against Chikungunya fever.

COMMITTEE MEMBERS:
Interno - 2412258 - EDILSON DANTAS DA SILVA JUNIOR
Externa à Instituição - KATYANNA SALES BEZERRA - UNICAMP
Presidente - 1352009 - UMBERTO LAINO FULCO
Externa à Instituição - ÉRIKA GEICIANNY DE CARVALHO MATIAS