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

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.

The Organochalcogen Compound (MeOPhSe)2 Inhibits Both Formation and the Viability of the Biofilm Produced by Candida albicans, at Different Stages of Development.

BACKGROUND: Candida albicans is a commensal and opportunistic fungus which is able to produce both local and systemic infections in immunocompromised patients. A correlation has been demonstrated between the resistance to conventional antifungal drugs and C. albicans ability to produce biofilms. Therefore, the potential of the organochalcogen compounds as antifungal therapy has been demonstrated. METHOD: In this work, we studied the effect of the organochalcogen compound (MeOPhSe)2 on both formation and the viability of the biofilm produced by C. albicans, at different stages of development. Biofilm formation and viability were determined by a metabolic assay based on the reduction of XTT assay. In addition, the morphology of the biofilm was observed using light microscopy. RESULTS: A significant reduction was observed in both growth and biofilm formation by C. albicans, in a dependent manner of cell density. In the presence of 2 µM (MeOPhSe)2 it was observed an inhibition of 87, 72, 69 and 56 % in C. albicans growth, using cell densities of 104, 105, 106 and 107 cells/mL, respectively. C. albicans growth was inhibited >90 % in the presence of 10 µM (MeOPhSe)2 in all cell densities used. Also, (MeOPhSe)2 was found to be able to decrease the viability of the biofilm produced by C. albicans at different stages of development. This effect was more pronounced in early biofilms as compared to mature biofilms. Biofilms forming at 6 and 12 hours was inhibited ~80% in the presence of 10 µM (MeOPhSe)2. However, mature biofilms presented an inhibition of ~40 % in the presence of 10 µM (MeOPhSe)2. The analyses of the structure of the biofilm have shown a significant reduction in the number of both yeast and filamentous form after treatment with (MeOPhSe)2. In addition, the organochalcogen compound (MeOPhSe)2 did not modify the viability of Fibroblastic cells. CONCLUSION: Taken together, these results demonstrated the potential of the organochalcogen compound (MeOPhSe) 2 as a promising antifungal therapy.