Toxicological evaluation of zidovudine and novel chalcogen derivatives in <i>Drosophila melanogaster</i>

Michelotti, Paula; Gonçalves, Débora Farina; Duarte, Tâmie; Sarturi, Joelma M; Silva, Rafael S. da; Rodrigues, Oscar E. D.; Rocha, João Batista Teixeira da; Corte, Cristiane Lenz Dalla

doi:10.1002/jbt.23356

Cited by 3 publications

(1 citation statement)

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“…Synthetic compounds containing chalcogen atoms have been the subject of several studies due to their broad biological properties [ 70 , 71 ]. The performance of organoselenium, organotellurium, and organosulfur against free radicals, as well as their effectiveness as antiviral, anti-inflammatory, and antitumor agents, has directed many scientific studies [ 72 , 73 , 74 ].…”

Section: Resultsmentioning

confidence: 99%

Antiviral Effect of 5′-Arylchalcogeno-3-aminothymidine Derivatives in SARS-CoV-2 Infection

Tucci,

da Rosa,

Rosa

et al. 2023

Molecules

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The understanding that zidovudine (ZDV or azidothymidine, AZT) inhibits the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and that chalcogen atoms can increase the bioactivity and reduce the toxicity of AZT has directed our search for the discovery of novel potential anti-coronavirus compounds. Here, the antiviral activity of selenium and tellurium containing AZT derivatives in human type II pneumocytes cell model (Calu-3) and monkey kidney cells (Vero E6) infected with SARS-CoV-2, and their toxic effects on these cells, was evaluated. Cell viability analysis revealed that organoselenium (R3a–R3e) showed lower cytotoxicity than organotellurium (R3f, R3n–R3q), with CC50 ≥ 100 µM. The R3b and R3e were particularly noteworthy for inhibiting viral replication in both cell models and showed better selectivity index. In Vero E6, the EC50 values for R3b and R3e were 2.97 ± 0.62 µM and 1.99 ± 0.42 µM, respectively, while in Calu-3, concentrations of 3.82 ± 1.42 µM and 1.92 ± 0.43 µM (24 h treatment) and 1.33 ± 0.35 µM and 2.31 ± 0.54 µM (48 h) were observed, respectively. The molecular docking calculations were carried out to main protease (Mpro), papain-like protease (PLpro), and RdRp following non-competitive, competitive, and allosteric inhibitory approaches. The in silico results suggested that the organoselenium is a potential non-competitive inhibitor of RdRp, interacting in the allosteric cavity located in the palm region. Overall, the cell-based results indicated that the chalcogen-zidovudine derivatives were more potent than AZT in inhibiting SARS-CoV-2 replication and that the compounds R3b and R3e play an important inhibitory role, expanding the knowledge about the promising therapeutic capacity of organoselenium against COVID-19.

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