Atividade antiviral in vitro de compostos naturais como potenciais alternativas contra o SARS-CoV-2

• Ano de defesa: 2023
• Autor(a) principal: Sousa, Vânia Carla de
• Orientador(a): Fernandes, Cléberson de Freitas
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS
• Link de acesso: http://repositorio.ufc.br/handle/riufc/78268

In March 2020, the World Health Organization (WHO) declared the Covid-19 pandemic, caused by the SARS-CoV-2 virus, becoming an unprecedented global problem in human health, social stability and, subsequently, a socioeconomic problem. Natural products and their structural molecules have historically contributed to pharmacotherapy, acting as a source of molecules with different biological activities, emphasizing their action against cancer, infectious diseases, and potent antiviral inhibitors. In this context, Brazilian biodiversity, given its richness, presents itself as a promising source in bioprospecting and in the development of molecules with potential biological applications. This work, the flavonoids: kaempferol and alpha-bisabolol, as well as vitamin E (alpha-tocopherol), were evaluated for their potential as an antiviral agent. For this purpose, in vitro assays were conducted to evaluate the cytotoxic potential of the molecules by MTT assays and, later, PRNT viral neutralization assays in Vero cell line against the Delta lineage of SAR-CoV-2. From the cytotoxicity assays, the concentrations were determined for each molecule with a cytotoxic potential lower than 30%, being 25, 6.25 and 6.25 mg/mL for alpha-tocopherol, kaempferol and alphabisabolol, respectively. These concentrations were used in viral neutralization assays. The PRNT viral neutralization results, when in direct contact with the virus, showed an inhibition percentage of 98.2%, 20.8% and 8.8% for alpha-tocopherol, kaempferol and alpha-bisabolol, respectively. To evaluate the possible mechanism of action of the molecule, in silico molecular docking assays were performed against three targets of viral RNA polymerase proteins RdRp, Mpro and Spike. In molecular anchoring, alphatocopherol obtained the best energy performance, followed by kaempferol and alphabisabolol, with the difference that alpha-tocopherol obtained a triple mode of action Mpro, RdRp and Spike. The present work presented the in vitro anti-SARS-CoV-2 antiviral activity of alpha-tocopherol, as well as its interaction with sites of importance in viral replication, which may indicate the potential of this molecule in the treatment of Covid-19, thus emphasizing the importance of studies aimed at establishing new alternatives for the discovery of antiviral agents.