Is There any Alternative Receptor for SARS-CoV-2?

Document Type : Letter to The Editor


1 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

2 Sernova Corp., London, Ontario, Canada

3 Laboratory of Pediatric Hepatology and Cell Therapy, Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Brussels, Belgium


Angiotensin-converting enzyme II (ACE2) in association with type II transmembrane serine protease (TMPRSS2) is considered the main receptor of SARS-CoV-2. However, considering the clinical complications of COVID-19 in different organs, there is no strong association between the abundance of ACE2/TMPRSS2 co-expression and clinical features of the disease and the severity of complications. Since SARS-CoV-2 affects certain organs that lack or have low expression of ACE2/TMPRSS2, it may be possible that the virus employs other receptors for colonization and entry. Based on recent studies, glucose-regulated protein 78 (GRP78) can be a potential alternative receptor for SARS-CoV-2 entry. In this letter, supporting evidence proposed GRP78 as an alternative receptor in SARS-CoV-2 infection.