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Mechanisms of SARS-CoV-2 entry into cells
Cody B Jackson1,2, Michael Farzan1, Bing Chen3,4
1Department of Immunology and Microbiology, Scripps Research, Jupiter, FL, USA.
Nature Reviews. Molecular Cell Biology
|October 6, 2021
Summary
This review details the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry mechanisms into host cells. Understanding spike protein binding to ACE2 and viral fusion is key for developing effective COVID-19 therapeutics.
Area of Science:
- Virology
- Structural Biology
- Cell Biology
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, necessitates understanding viral entry mechanisms.
- The spike (S) protein binding to angiotensin-converting enzyme 2 (ACE2) and subsequent membrane fusion are critical steps in viral entry.
Purpose of the Study:
- To provide a comprehensive review of the structural and cellular basis of SARS-CoV-2 entry.
- To elucidate the roles of key proteases and viral adaptations in host cell infection.
- To examine therapeutic strategies targeting viral entry.
Main Methods:
- Review of existing literature on SARS-CoV-2 structure and entry pathways.
- Analysis of structural data and cellular processes involved in viral fusion.
- Examination of host-receptor interactions and viral protein adaptations.
Main Results:
- Detailed description of S protein synthesis, structure, and conformational changes.
- Identification of the roles of furin-like proteases, TMPRSS2, and cathepsin L in S protein activation.
- Delineation of ACE2 orthologue features and S protein adaptations facilitating human transmission.
Conclusions:
- A thorough understanding of SARS-CoV-2 entry mechanisms is crucial for combating the pandemic.
- Targeting viral entry pathways offers promising therapeutic avenues.
- Further research is needed to address outstanding questions regarding viral entry and transmission.
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