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Is There any Alternative Receptor for SARS-CoV-2?
Mahtab Shahriari Felordi1, Arash Memarnejadian2, Mustapha Najimi3
1Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Cell Journal
|June 7, 2021
Summary
Glucose-regulated protein 78 (GRP78) may serve as an alternative entry receptor for SARS-CoV-2, the virus causing COVID-19. This finding challenges the sole reliance on ACE2/TMPRSS2 and explains infections in organs with low expression of these primary receptors.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- The primary SARS-CoV-2 entry pathway involves Angiotensin-converting enzyme II (ACE2) and transmembrane serine protease 2 (TMPRSS2).
- Clinical observations of COVID-19 complications in various organs do not consistently correlate with ACE2/TMPRSS2 co-expression levels.
- SARS-CoV-2 impacts organs with limited or absent ACE2/TMPRSS2, suggesting alternative viral entry mechanisms.
Discussion:
- Glucose-regulated protein 78 (GRP78) is proposed as a potential alternative receptor for SARS-CoV-2.
- GRP78's presence in various tissues may facilitate viral entry and colonization.
- This hypothesis addresses the discrepancy between ACE2/TMPRSS2 expression and COVID-19's multi-organ involvement.
Key Insights:
- Evidence supports GRP78 as an alternative SARS-CoV-2 receptor.
- This challenges the established ACE2/TMPRSS2-centric model of viral entry.
- GRP78 offers a new perspective on SARS-CoV-2 pathogenesis and tropism.
Outlook:
- Further research is needed to validate GRP78's role in SARS-CoV-2 infection.
- Investigating GRP78 could reveal new therapeutic targets for COVID-19.
- Understanding alternative receptors may explain differential disease severity and organ-specific manifestations.
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