| Congresso Brasileiro de Microbiologia 2023 | Resumo: 1184-1 | ||||
Resumo:The SARS-CoV-2 is the etiological agent for COVID-19 with global dissemination. Studies have been directed towards for the development of an effective treatment against COVID-19, mainly in critically ill hospitalized patients, helping to control the emergence of new coronavirus mutations. Ebselen (EbSe) is an organoselenium compound safe for humans and has antioxidant, anti-inflammatory and antimicrobial properties. Diphenyl diselenide ((PhSe)2) has similar chemical and pharmacological properties to EbSe. Herein, we compare EbSe and (PhSe)2 in vitro anti-SARS-CoV-2 activity, as well as its predictive mechanism of interaction with Mpro (virus main protease) in silico. Calu-3 (human type II pneumocytes) cells were infected with SARS-CoV-2 (GenBank MT710714, SisGen AC58AE2) at a multiplicity of infection (MOI) of 0.01 and 0.1 for 1 hour at 37°C. After that, the culture medium was removed, and treatment (0.78-12.5 µM) was performed for 24 and 48 hours. The replicative ability of SARS-CoV-2 in supernatant of infected cultures with or without treatment was evaluated by counting the plaque-forming units (PFU/mL), and the cytotoxicity was assessed by MTT assay. The EC50 values for EbSe and (PhSe)2 after 24 hours post infection (hpi) was 3.8 µM and 3.9 µM, respectively, and after 48 hpi were 2.6 µM and 3.4 µM. These concentrations are safe to non-infected cells, since CC50 found was greater than 200 µM, for both molecules. In silico data suggested that the antiviral mechanism of (PhSe)2 against SARS-CoV-2 occurs through covalent binding to C145 residue of Mpro. Our results indicate that EbSe and (PhSe)2 have a relevant inhibitory action against the replication of SARS-CoV-2 in vitro, demonstrating the functional importance of these compounds, and their scaffolds, in the development of possible therapeutic drugs for the COVID-19 treatment. At this moment, our studies are moving forward with water-soluble (PhSe)2 analogues and its antiviral and anti-inflammatory properties. Palavras-chave: antiviral activity, COVID-19, organoselenium compounds, SARS-CoV-2 Agência de fomento:CAPES, CNPq, FAPERJ, IOC-FIOCRUZ | |||||