Enhanced Endoplasmic Reticulum Stress due to Severe Acute Respiratory Syndrome Coronavirus -2 Delta Strain could Induce Cytokine Storm Causing More Clinical Severities/Mortalities

Severe Acute Respiratory Distress Syndrome Coronavirus 2 (SARS-CoV-2) is one of the fast-replicating viruses known till date and with many variants reported all across the world. During the events of its replication and multiplication inside the host cell, it causes Endoplasmic Reticulum stress and activates the host intracellular defense mechanism, Unfolded Protein Response (UPR) to limit the replication and protein synthesis processes. The deep pathophysiology of IRE1alpha during viral infection and its intracellular defense mechanism is not fully clear. At the time of ER stress, the Inositol requiting enzyme 1 alpha (IRE1-alpha) activates both pro-survival and pro-apoptotic cellular responses. It also triggers the interferon production. Due to ongoing viral protein synthesis, the hosts’ protein translation is hindered and this may lead to programmed cell death. In case of SARS-CoV-2 infection caused by different variants in different host, we predict that these events may differ. Hence, to understand the variant specific cellular pathogenicity of the SARS-CoV-2 we performed the quantitative ELISA of IRE-1 antigen in Wuhan, Delta and Omicron variants in cultured Vero E6 cells. This study i.e. IRE1-alpha intracellular defense mechanism against SARS-CoV-2 was also confirmed using bioinformatic tools.