Diphenyl diselenide and cidofovir present anti-viral activity against Bovine Alphaherpesvirus 2 in vitro and in a sheep model

Amaral, Bruna Portolan; Cargnelutti, Juliana Felipetto; Mortari, Ana Paula Gnocato; Merchioratto, Ingryd; Feio, L.M.; Nogueira, Cristina Wayne; Weiblen, Rudi; Flores, Eduardo Furtado

doi:10.1016/j.rvsc.2020.11.023

Cited by 4 publications

(5 citation statements)

References 35 publications

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“…Importantly, one of the first computational experimental screenings toward SARS-CoV-2 identified Eb as one of the most promising inhibitors of the protease Mpro, as well as a potent inhibitor of the enzyme in vitro and of SARS-CoV-2 replication [ 17 , 18 ]. The antiviral activity of (PhSe) 2 is less explored, but there is evidence of its efficacy against other viruses, including the herpes simplex virus 2 (HSV-2) and the bovine alphaherpesvirus 2 (BoHV-2) [ 19 , 20 , 21 ]. Moreover, our group has already demonstrated that (PhSe) 2 is capable of covalently interacting with the SARS-CoV-2 Mpro in silico and inhibiting virus replication in a Vero E6 cell model.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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)2) shares several pharmacological properties with Eb and is of low toxicity to mammals. Herein, we investigated Eb and (PhSe)2 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 EC50 values for Eb and (PhSe)2 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 CC50 values found for Eb and (PhSe)2 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)2 as a new candidate to be tested in future trials against SARS-CoV-2 infection/inflammation conditions.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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“…[334] Infections have been defined as a disease caused by pathogenic microorganisms, such as parasites, fungi, bacteria, or virus. [334] Diorganyl diselenides have demonstrated significant effectiveness in preclinical investigations against infectious diseases, displaying antiparasitic, [335][336][337] antifungal, [338][339][340][341][342][343][344][345] antibacterial, [346,347] and antiviral [348,349] actions in preclinical research. [336,339,342,347,348] Figure 2 illustrates pathogenic microorganisms that are targeted by diorganyl diselenides.…”

Section: Diorganyl Diselenides As Antimicrobial Agentsmentioning

confidence: 99%

“…[354] The antiviral activity of diphenyl diselenide against BoHV-2 was demonstrated in vitro and in a sheep model. [348] In parasitic diseases, the World Health Organization reports Leishmaniasis, as a significant public health concern, with 0.7-1 million new cases reported annually. [355] Studies suggest that diorganyl diselenides, exhibiting leishmanicidal activities, hold promise as a treatment for Leishmaniasis caused by Leishmania infantum, demonstrating low in vitro cytotoxicity.…”

Section: Diorganyl Diselenides As Antimicrobial Agentsmentioning

confidence: 99%

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Recent Progress in Synthetic and Biological Application of Diorganyl Diselenides

do Carmo Pinheiro,

Souza Marques,

Ten Kathen Jung

et al. 2024

The Chemical Record

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Diorganyl diselenides have emerged as privileged structures because they are easy to prepare, have distinct reactivity, and have broad biological activity. They have also been used in the synthesis of natural products as an electrophile in the organoselenylation of aromatic systems and peptides, reductions of alkenes, and nucleophilic substitution. This review summarizes the advancements in methods for the transformations promoted by diorganyl diselenides in the main functions of organic chemistry. Parallel, it will also describe the main findings on pharmacology and toxicology of diorganyl diselenides, emphasizing anti‐inflammatory, hypoglycemic, chemotherapeutic, and antimicrobial activities. Therefore, an examination detailing the reactivity and biological characteristics of diorganyl diselenides provides valuable insights for academic researchers and industrial professionals.

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“…Diselenides are an important class of organoselenium compounds that have been studied mainly for their antioxidant and anti-inflammatory potential. − (PhSe) 2 is the parent compound of diaryl diselenides and displays weak electrophilic potential. , Conversely, in terms of electrophilicity, ebselen, which is a selenenylamide, possesses strong electrophilic potential . The toxicological and pharmacological interaction of (PhSe) 2 with different targets has been studied in silico ,,− and in vitro , and antiviral , and antifungal activity was reported. Thus, (PhSe) 2 is interesting because it represents an archetypal model or scaffold of diselenide compounds and because it is a renowned potential therapeutic agent with inhibitory potency against M pro in the low micromolar range and, consequently, has pharmacological significance .…”

Section: Introductionmentioning

confidence: 99%

Diphenyl Diselenide and SARS-CoV-2: in silico Exploration of the Mechanisms of Inhibition of Main Protease (M^pro) and Papain-like Protease (PL^pro)

Omage

Madabeni

Tucci

et al. 2023

J. Chem. Inf. Model.

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The SARS-CoV-2 pandemic has prompted global efforts to develop therapeutics. The main protease of SARS-CoV-2 (Mpro) and the papain-like protease (PLpro) are essential for viral replication and are key targets for therapeutic development. In this work, we investigate the mechanisms of SARS-CoV-2 inhibition by diphenyl diselenide (PhSe)2 which is an archetypal model of diselenides and a renowned potential therapeutic agent. The in vitro inhibitory concentration of (PhSe)2 against SARS-CoV-2 in Vero E6 cells falls in the low micromolar range. Molecular dynamics (MD) simulations and density functional theory (DFT) calculations [level of theory: SMD-B3LYP-D3(BJ)/6-311G(d,p), cc-pVTZ] are used to inspect non-covalent inhibition modes of both proteases via π-stacking and the mechanism of covalent (PhSe)2 + Mpro product formation involving the catalytic residue C145, respectively. The in vitro CC50 (24.61 μM) and EC50 (2.39 μM) data indicate that (PhSe)2 is a good inhibitor of the SARS-CoV-2 virus replication in a cell culture model. The in silico findings indicate potential mechanisms of proteases’ inhibition by (PhSe)2; in particular, the results of the covalent inhibition here discussed for Mpro, whose thermodynamics is approximatively isoergonic, prompt further investigation in the design of antiviral organodiselenides.

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Diphenyl diselenide and cidofovir present anti-viral activity against Bovine Alphaherpesvirus 2 in vitro and in a sheep model

Cited by 4 publications

References 35 publications

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

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

Recent Progress in Synthetic and Biological Application of Diorganyl Diselenides

Diphenyl Diselenide and SARS-CoV-2: in silico Exploration of the Mechanisms of Inhibition of Main Protease (M^pro) and Papain-like Protease (PL^pro)

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Diphenyl diselenide and cidofovir present anti-viral activity against Bovine Alphaherpesvirus 2 in vitro and in a sheep model

Cited by 4 publications

References 35 publications

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

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

Recent Progress in Synthetic and Biological Application of Diorganyl Diselenides

Diphenyl Diselenide and SARS-CoV-2: in silico Exploration of the Mechanisms of Inhibition of Main Protease (Mpro) and Papain-like Protease (PLpro)

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Diphenyl Diselenide and SARS-CoV-2: in silico Exploration of the Mechanisms of Inhibition of Main Protease (M^pro) and Papain-like Protease (PL^pro)