Endoplasmic reticulum secretory pathway: Potential target against SARS-CoV-2

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged throughout the world, resulting in more than 400 million cases and over 6 million deaths worldwide as of January 2022. Coronaviruses subvert or use certain aspects of the unfolded protein response in the endoplasmic reticulum to overcome protein translation shutdown to benefit their replication. New virions use the ER-Golgi intermediate compartment to assemble and gain transportation to the cell membrane. Extensive remodeling of the ER has been demonstrated during SARS-CoV-2 infection. In this review article, we discuss the role of the endoplasmic reticulum secretory pathway in the replication cycle of SARS-CoV-2. Currently, there is a dearth of therapeutic options for intervening with SARS-CoV-2 infection. To accelerate drug development, efforts around the globe have been focusing on repurposing drugs that have already been approved for clinical use by regulatory agencies. Targeting the ERS pathway is reasonable, as prior work has shown that SARS-CoV-2 egress is dependent on this pathway. Here we discuss the feasibility of off-patent, FDA-approved, pharmacological inhibitors of the ERS pathway to suppress the SARS-CoV-2 replication cycle, a promising approach that warrants investigation.