Modelos experimentais que simulam a digestão proteolítica humana e prospecção in sílico de peptídeos derivados do inibidor de tripsina purificado de sementes de tamarindo com potencial anti-SARS-CoV-2

Abstract

The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2, is a serious threat to healthcare systems worldwide. In this context, several studies have been developed with protease inhibitors and their derivatives to investigate their bioactive effects, such as antiviral, antiinflammatory, and satietogenic functions, among others. Thus, whereas proteins are sources of biological products that can be used for the control and treatment of various human diseases, such as COVID-19, we investigated experimental models that mimic human digestion and prospected 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. For SR, 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 (IPE=-287.48 kJ.mol-1. SD=199,67) and its analogue peptide (IPE=-293.49 kJ.mol-1. SD=171,95). Thus, both peptides had many hydrophobic residues, a common physicalchemical property among peptides that inhibit the entry of enveloped viruses, such as SARSCov-2, present in drugs used to treat of diseases related to these viruses. Therefore, this research presents an expressive scientific contribution, since the SR grouped important data that will provide subsidies for development of studies in vitro, in vivo and in sílico related to the clinical application of bioactive peptides. Therefore, being a guideline for carrying out the theoretical cleavage of TTIp 56/287, that triggered potential candidates for agents that inhibit SARS-CoV-2 infection, from the 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, in order to assist the scientific community in promoting health and in the development of similar studies with other plant sources.