Banca de DEFESA: ANNA BEATRIZ SANTANA LUZ

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : ANNA BEATRIZ SANTANA LUZ
DATE: 23/01/2023
TIME: 08:00
LOCAL: Videoconferência - Link para acesso: https://meet.google.com/vgd-wqrn-hbe
TITLE:

Experimental models that simulate human proteolytic digestion and in silico prospecting of peptides derived from purified trypsin inhibitor from tamarind seeds with anti-SARS-CoV-2 potential

KEY WORDS:

Antivirals; coronavirus; digestion; protease inhibitors; pandemic; tamarind.

PAGES: 90
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Proteins are multifunctional macromolecules and also act as sources of amino acids and energy. Protein hydrolysis also generates numerous bioactive peptides with different functions in the body. In this context, proteins are sources of biological products that can be used for the control and treatment of various human diseases, and may be candidates for the management and treatment of diseases such as COVID-19. To investigate experimental models that mimic human digestion and prospect peptides from trypsin inhibitor purified from tamarind (TTIp) seeds. The first two chapters of this study are referring to a systematic review (SR), and are organized as follows: the first chapter presents the SR protocol registered in the International Prospective Register of Systematic Reviews (under number CRD42020198709); and the second chapter is the SR of in vitro studies that used methodological procedures to mimic the gastrointestinal digestion of proteins. Articles were selected according to the study population, interventions, control, results and type of study strategy. The searches were carried out in Pubmed, Web of Science, Science direct, Embase, Virtual Health Library and Scopus databases. The methodological quality assessment was performed using the Office of Health Assessment and Translation tool. A total of 1.986 articles were selected, resulting in 20 eligible studies. In the results section, we describe the methodological procedures used in vitro to simulate the digestion of animal or vegetable proteins. The third chapter refers to an in silico prospecting study of native peptides and analogues with anti-SARS-Cov-2 potential, derived from TTIp. Native peptides were obtained from enzymatic cleavages of TTIp in silico and analogues were generated by replacing amino acids in the primary sequences of native peptides. The anti-SARS-CoV-2 potential was investigated by simulating molecular dynamics between the peptides and the binding sites of transmembrane serine protease 2 (TMPRSS2), necessary for the entry of SARS-CoV-2 into the host cell, and generated a patent application: BR 10 2022 020330 0. The best interaction potential energy occurred between TMPRSS2 and one of the native peptides obtained by cleavage with trypsin (-287.48 kJ.mol^-1) and its analogue peptide (-293.49 kJ.mol^-1). Thus, both peptides had many hydrophobic residues, a common physical-chemical property among peptides that inhibit the entry of enveloped viruses, such as SARS-Cov-2, present in drugs used to treat of diseases related to these enveloped viruses. Therefore, this research presents an expressive scientific contribution, since the SR grouped important data that will provide subsidies for development of studies related to the clinical application of bioactive peptides, concluding that, although in vitro dynamic experimental models are more accurate, static models can be used to simulate human proteolytic digestion, provided that the physiological conditions are controlled and there is a comparison with in vivo studies to ensure greater accuracy of the results. In addition, the in silico study resulted, from the cleavage of TTIp 56/287, in potential candidates for agents that inhibit SARS-CoV-2 infection, through interaction with TMPRSS2, encouraging future in vitro and in vivo investigations that aim to use the peptides prospected here as specific medicines for the treatment of COVID-19 and other diseases.

COMMITTEE MEMBERS:
Interna - 1549705 - ADRIANA FERREIRA UCHOA
Externo à Instituição - ALEXANDRE COELHO SERQUIZ - UNI-RN
Presidente - 2578619 - ANA HELONEIDA DE ARAUJO MORAIS
Externo ao Programa - 1959889 - DAVI SERRADELLA VIEIRA - nullExterna à Instituição - RICHELE JANAINA ARAUJO MACHADO - UNICHRISTUS