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Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in more than 4.4 million deaths worldwide as of August 24, 2021. Viral infections such as SARS-CoV2 are associated with endoplasmic reticulum (ER) stress and also increased the level of reactive oxygen species. Activating transcription factor 4 (ATF4) is preferentially translated under integrated stress conditions and controls the genes involved in protein homeostasis, amino acid transport and metabolism, and also protection from oxidative stress. The GRP78, regulated either directly or indirectly by ATF4, is an essential chaperone in the ER and overexpressed and appears on the surface of almost all cells during stress and function as a SARS-CoV2 receptor. In this mini-review article, we briefly discuss the effects of SARS-CoV2 infection on the ER stress, and then the stress modulator functions of ATF4 and GRP78 as novel therapeutic targets were highlighted. Finally, the effects of GRP78 inhibitory components as potential factors for targeted therapies for COVID-19 critical cases were discussed. [ABSTRACT FROM AUTHOR]

Bee venom (BV) has variety of properties, such as anti-inflammatory potential and anti-cancer activity.It has been shown that BV has cytotoxic effects on MCF-7 cells in 2D culture. Cell encapsulation is one of the three-dimensional (3D) culture methods that can better represent the physiological conditions of natural tissues and tumors in comparison to two-dimensional (2D) culture. However, the effect of BC on 3D culture has yet studied. The present study was designed to compare the cytotoxic effects of BV on MCF-7 cells in 3D and 2D cultures for the first time. To this purpose, the MCF-7 cells were encapsulated to create a 3D culture using alginate hydrogel, a natural polysaccharide. Cytotoxicity effect of BV was investigated using 3-(4,5-Dimethylthiazoyl-2-yl)-2,5-Diphenyltetrazolium bromide (MTT) reduction and confirmed with neutral red uptake assay following venom exposure. Apoptosis was evaluated with reactive nitrogen species assay, measuring Caspase-3 activity and Comet assay. Moreover, oxidative stress was evaluated by glutathione (GSH) and catalase assays. Results of caspase-3 and comet assays showed an increase of tumoral cells apoptosis following the treatment with venom in a dose dependent manner in both 2D and 3D cultures. GSH and catalase measurements showed that oxidative stress was increased in MCF-7 cells treated with BV in a dose dependent manner in both 2D and 3D cultures. The results of the present study show that the crude venom of Apis mellifera has cytotoxic effects on MCF-7 cells in a dose dependent manner. Indeed, it was shown that the effect of the venom on MCF-7 cells in 2D culture is significantly higher than that of the 3D culture. [ABSTRACT FROM AUTHOR]