Ebselen and Diphenyl Diselenide Inhibit SARS-CoV-2 Replication at Non-Toxic Concentrations to Human Cell Lines

• Published in: Vaccines (Basel) Vol. 11; no. 7; p. 1222
• Main Authors: Wildner, Guilherme, Tucci, Amanda Resende, Prestes, Alessandro de Souza, Muller, Talise, Rosa, Alice Dos Santos, Borba, Nathalia Roberto R, Ferreira, Vivian Neuza, Rocha, João Batista Teixeira, Miranda, Milene Dias, Barbosa, Nilda Vargas
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.07.2023; MDPI
• Subjects: anti-SARS-CoV-2 activity; antiviral; Antiviral agents; Cell cycle; Cell lines; Clinical trials; Coronaviruses; COVID-19; Cytokines; diphenyl diselenide; Disease transmission; ebselen; Enzymes; FDA approval; Immune system; Infections; Inflammation; Leukocytes (mononuclear); lymphocytes; Organoselenium compounds; organoselenium molecules; Pandemics; Peripheral blood mononuclear cells; Pneumocytes; Proteins; Public health; Replication; Respiratory diseases; Severe acute respiratory syndrome coronavirus 2; Toxicity; Viral diseases; Viruses; Brazil; United States > US; anti-SARS-CoV-2 activity; ebselen; organoselenium molecules; lymphocytes; diphenyl diselenide; antiviral
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines11071222

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the causative agent of the COVID-19 pandemic, a global public health problem. Despite the numerous studies for drug repurposing, there are only two FDA-approved antiviral agents (Remdesivir and Nirmatrelvir) for non-hospitalized patients with mild-to-moderate COVID-19 symptoms. Consequently, it is pivotal to search for new molecules with anti-SARS-CoV-2 activity and to study their effects in the human immune system. Ebselen (Eb) is an organoselenium compound that is safe for humans and has antioxidant, anti-inflammatory, and antimicrobial properties. Diphenyl diselenide ((PhSe) ) shares several pharmacological properties with Eb and is of low toxicity to mammals. Herein, we investigated Eb and (PhSe) anti-SARS-CoV-2 activity in a human pneumocytes cell model (Calu-3) and analyzed their toxic effects on human peripheral blood mononuclear cells (PBMCs). Both compounds significantly inhibited the SARS-CoV-2 replication in Calu-3 cells. The EC values for Eb and (PhSe) after 24 h post-infection (hpi) were 3.8 µM and 3.9 µM, respectively, and after 48 hpi were 2.6 µM and 3.4 µM. These concentrations are safe for non-infected cells, since the CC values found for Eb and (PhSe) on Calu-3 were greater than 200 µM. Importantly, the concentration rates tested on viral replication were not toxic to human PBMCs. Therefore, our findings reinforce the efficacy of Eb and demonstrate (PhSe) as a new candidate to be tested in future trials against SARS-CoV-2 infection/inflammation conditions.