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. Keywords COVID-19 disease • ER stress modulation • ATF4 • GRP78 targeting COVID-19 infection and ER stressThe SARS-CoV-2 is a member of Coronaviridae, a kind of enveloped viruses with positive-sense, single-stranded RNA [1]. This virus caused more than 4.4 million deaths worldwide up to August 2021. No specific therapeutic treatment for COVID-19 has been approved so far which highlighting the urgent need to identify new antiviral strategies.

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The production and secretion of defense proteins are one of the protective mechanisms exploited by plants against pathogens. The production and secretion of defense proteins are one of the protective mechanisms exploited by plants against pathogens. Ribosome-Inactivating Proteins (RIPs), as the main class of these proteins, are considered to facilitate cancer therapy worldwide, because of the potential anticancer activity. Indeed, some of these proteins have cytotoxic and anticancer properties. Extracted from the carnation (Dianthus caryophyllus), Dianthin inhibits protein synthesis in many different cells. Methods: In this research, the Dianthins was isolated and purified from the leaves of D. caryophyllus, using ion-exchange chromatography column (CM-Sephadex G-50). Subsequently, its cytotoxicity effect on MCF-7 cell line was investigated. The cell cytotoxicity assessment was performed, using 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT), neutral red uptake, and alkaline comet assays at the concentrations of 1.25μg/ mL to 10μg/mL of the protein applying the MCF-7 cell line. Results: the toxin induces cell death, mostly via necrosis rather than apoptosis, but in the special range of concentrations. Conclusion: because of the severe side effects of chemotherapy drugs, this toxin can undergo more research as a new drug candidate against breast cancer.

Recurrence in hepatocellular carcinoma (HCC) after conventional treatments is a crucial challenge. Despite the promising progress in advanced targeted therapies, HCC is the fourth leading cause of cancer death worldwide. Radionuclide therapy can potentially be a practical targeted approach to address this concern. Rhenium-188 (188Re) is a β-emitting radionuclide used in the clinic to induce apoptosis and inhibit cell proliferation. Although adherent cell cultures are efficient and reliable, appropriate cell-cell and cell-extracellular matrix (ECM) contact is still lacking. Thus, we herein aimed to assess 188Re as a potential therapeutic component for HCC in 2D and 3D models. The death rate in treated Huh7 and HepG2 lines was significantly higher than in untreated control groups using viability assay. After treatment with 188ReO4, Annexin/PI data indicated considerable apoptosis induction in HepG2 cells after 48 h but not Huh7 cells. Quantitative RT-PCR and western blotting data also showed increased apoptosis in response to 188ReO4 treatment. In Huh7 cells, exposure to an effective dose of 188ReO4 led to cell cycle arrest in the G2 phase. Moreover, colony formation assay confirmed post-exposure growth suppression in Huh7 and HepG2 cells. Then, the immunostaining displayed proliferation inhibition in the 188ReO4-treated cells on 3D scaffolds of liver ECM. The PI3-AKT signaling pathway was activated in 3D culture but not in 2D culture. In nude mice, Huh7 cells treated with an effective dose of 188ReO4 lost their tumor formation ability compared to the control group. These findings suggest that 188ReO4 can be a potential new therapeutic agent against HCC through induction of apoptosis and cell cycle arrest and inhibition of tumor formation. This approach can be effectively combined with antibodies and peptides for more selective and personalized therapy.