Banca de QUALIFICAÇÃO: DANIEL MELO DE OLIVEIRA CAMPOS

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : DANIEL MELO DE OLIVEIRA CAMPOS
DATE: 22/08/2024
TIME: 19:00
LOCAL: Videoconferência - Link para acesso: https://meet.google.com/wqk-vrax-xgw
TITLE:

Development of Multi-Epitope Vaccine and Potential Inhibitors of Sars-Cov-2 Mpro Protease: Reverse Vaccinology and Computational Chemistry Approaches

KEY WORDS:

Sars-CoV-2; Multi-epitope vaccine; Non-covalent inhibitor; Mpro protease; Computational chemistry

PAGES: 127
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Infections caused by SARS-CoV-2 have posed a significant threat to global public health and continue to be a relevant and complex issue. This thesis aimed to explore new approaches to combating the virus, focusing on the development of a multi-epitope vaccine and the identification of potential Mpro protease inhibitors. Two in silico studies were conducted: one dedicated to the design of a multi-epitope vaccine using reverse vaccinology, and the other focused on developing non-covalent inhibitors through computational chemistry. Additionally, the thesis includes a critical review of emerging antiviral strategies. The first chapter of this thesis presents a critical commentary on promising targets and pharmacological strategies adopted during the pandemic. Among the main targets were Mpro, the S glycoprotein, and TMPRSS2. It concludes that, despite advancements, definitive evidence on the efficacy of these treatments was still necessary. Meanwhile, repurposing existing drugs and using convalescent plasma remained the best alternatives until an effective vaccine was developed. In the second chapter, we conducted an in silico study to develop a new multi-epitope vaccine against SARS-CoV-2, including the Alpha, Beta, Gamma, Delta, and Omicron variants. We used an immunoinformatics approach to identify the best immunogenic epitopes from the four structural proteins of the virus (S, M, N, and E) from 475 genomes sequenced from regions with high disease incidence. The vaccine was modeled, refined, validated, and its molecular docking with the TLR3 receptor was evaluated. The results suggest that the candidate vaccine increases antibody response and should be tested in clinical trials. In the third chapter, we evaluated and compared two potential non-covalent inhibitors of SARS-CoV-2 Mpro, WU-04 and ML188, using computational chemistry approaches, including quantum calculations and ADMET analysis. Our results revealed that residues Met165, Asn142, Glu166, His41, and Leu141 are critical as they interact with high affinity with both inhibitors, suggesting that these residues are essential for complex stabilization. The total energy calculated for the Mpro-WU-04 complex was -52.21 kcal/mol, while for Mpro-ML188, it was -40.47 kcal/mol, indicating that the WU-04 inhibitor has greater energetic affinity.

COMMITTEE MEMBERS:
Presidente - 2412258 - EDILSON DANTAS DA SILVA JUNIOR
Externa à Instituição - JÉSSICA DE FÁTIMA VIANNA - UERN
Externa à Instituição - KATYANNA SALES BEZERRA - UNICAMP