Banca de DEFESA: DANDARA DE PAULA CANDIDO

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : DANDARA DE PAULA CANDIDO
DATE: 21/06/2023
TIME: 14:00
LOCAL: https://conferenciaweb.rnp.br/webconf/carlos-mauricio-rabello-de-santanna
TITLE:

Semi-empirical PM7 Study of Complexes Between SARS-CoV-2 Spike RBD with hACE2 Peptides, Candidate Inhibitors of Viral Infection

KEY WORDS:

Covid-19. Spike. hACE2-derived peptides. PM7. Covalent inhibition.

PAGES: 93
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SUMMARY:

At the end of 2019, the world experienced a new viral disease, currently called COVID-19, caused by the coronavirus SARS-CoV-2. COVID-19 has spread rapidly around the world, causing more than 6.94 million deaths to date. Among the proteins of SARS-CoV-2, Spike has aroused special interest, since the coronavirus uses it to bind through the receptor binding domain (RBD) to the converting enzyme of human angiotensin 2 (hACE2), thus initiating invasion into the host cell. A recent in vitro study demonstrated that hACE2-derived peptides containing the amino acid sequence EDLFYQ (SAP1, SAP2 and SAP6) are able to inhibit Spike-mediated viral infection. The objective of this project is to employ theoretical methods to investigate the interaction mode of these peptides with Spike’s RBD, in order to obtain information for the rational design of new peptides, candidates for SARS-CoV-2 infection inhibitors, exploring the covalent inhibition strategy. Because it involves the formation of covalent bonds, the study was conducted using the semi-empirical quantum method PM7, which is fast enough to be applied to whole proteins and their complexes. All calculations involved the complete RBD, using the continuum approach to include the effect of the external environment on energy minimization, without structural constraints. The proposal of the new peptides was based on the chemistry of sulfur-triazole exchange (SuTEx), which allows selectivity for the formation of covalent bonds with tyrosine residues. The SAPs were modified by the incorporation of warhead groups sulfonyl-triazole, and a new proposed warhead group, phosphonyl-triazole, in order to increase the efficiency of the interaction through covalent bond formation. ΔHint calculated correlated with experimentally determined Kd for SAP1, SAP2 and SAP6, and confirm the SAP1 peptide both in native and in SuTEx-type modifications as best candidates for RBD ligands, followed by SAPs 6 and 2, in this order. It was also observed that the covalent complexes formed by SAP1 derivatives containing sulfonyl-triazole warhead groups have a greater tendency to be formed in the medium in which they were studied than those containing phosphonyl-triazole warheads.

COMMITTEE MEMBERS:
Presidente - 1220404 - CARLOS MAURICIO RABELLO DE SANT ANNA
Interna - 387189 - AUREA ECHEVARRIA AZNAR NEVES LIMA
Externa à Instituição - NELILMA CORREIA ROMEIRO - UFRJ