Avaliação biológica de organocalcogênios em Caenorhabditis elegans: uma possível terapia contra a covid-19

• Ano de defesa: 2024
• Autor(a) principal: Viçozzi, Gabriel Pedroso
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Brasil; Bioquímica; UFSM; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica; Centro de Ciências Naturais e Exatas
• Palavras-chave em Português: SARS-CoV-2; Selênio; Nanocápsula; Mpro; Modelo alternativo; Antioxidante; Selenium; Nanocapsules; Antioxidant; Alternative model; CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/33150

The new coronavirus (SARS-CoV-2) emerged in 2019 in Wuhan and, due to the urgency to find a cure, studies to develop vaccines were carried out and finally in 2021 the first batches were distributed. Due to the impossibility of some individuals receiving the vaccine (allergies, for example), there is a need to develop new therapies that are safe and effective. Among the proposed candidates are organochalcogen compounds derived from zidovudine (AZT) and ebselen (EBS) that have proven effective in in vitro and in silico studies. In this thesis, we objectively evaluated, through bioinformatic analysis, the inhibitory capacity of the main viral protein Protease (Mpro) of six AZT organochalcogen compounds, as well as the development of a nanoformulation containing EBS (NEBS) and the toxicological evaluation and antioxidant effect therefore, using the free-living nematode Caenorhabditis elegans as an animal model. The results of the first study demonstrated that no toxicity was found in any of the molecules in the concentration ranges tested in acute and chronic exposures. The in silico results showed that the AZTderived molecules interacted with important Mpro sites of SARS-CoV-2 in silico. They were able to interact with the antioxidant enzyme SOD-3 and the detoxifying enzyme GST-4, in addition to modulating the nuclear translocation of DAF-16. In the end, two molecules were chosen as most promising (S116h and S116l). In the second study, the development of the nanocapsule containing ebselen was completed with adequate physicochemical characteristics. In vivo tests indicated that the nanoformulation did not present toxicity to nematodes in the concentration and exposure range evaluated in relation to free EBS. In addition to presenting antioxidant activity since both treatments reduced ROS levels. In addition, EBS and NEBS decreased total time levels and interacted with the GST-4 enzyme. With these data we can conclude that both studies showed evidence of promising molecules for future studies for the development of new molecules against Covid-19.