The stress-inducible ER chaperone GRP78/BiP is upregulated during SARS-CoV-2 infection and acts as a pro-viral protein

Year: 2022

Type: article

Abstract: The current Coronavirus global pandemic necessitates the search for novel targets and therapeutic avenues. Shaban et al. 1 reported the use of an endoplasmic reticulum (ER) stress inducer thapsigargin (Tg) to block replication of Coronaviruses (CoVs), and that a key mechanism for the anti-viral activities of Tg is to counteract virus-mediated GRP78/BiP downregulation. This conclusion contradicts the widely observed upregulation of GRP78 by virus infection and the reported pro-viral roles of GRP78 2 , 3 . In contrast to their findings which were based primarily on short term culture of infected cells, here we have documented the temporal increase of both GRP78 mRNA and protein levels as SARS-CoV-2 infection intensifies, and that GRP78 knockdown or inhibition of its activity suppresses SARS-CoV-2 replication and infectivity in vitro and in vivo, implying that GRP78 could be a valuable stable host target to combat COVID-19.

Source: Nature Communications

DOI: 10.1038/s41467-022-34065-3

Authors: Woo-Jin Shin, Dat P. Ha, Keigo Machida, Amy S. Lee

Institutions: Cleveland Clinic, University of Southern California, USC Norris Comprehensive Cancer Center

Language: English

Topic: Endoplasmic Reticulum Stress and Disease

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,890

Funders: U.S. Department of Health and Human Services, W. M. Keck Foundation, Hastings Foundation, Korea Research Institute of Bioscience and Biotechnology, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Cancer Institute, Center for Information Technology

OpenAlex ID: W4309001629