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.