Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic, is a novel coronavirus that has caused significant global health concern. A key aspect of its virulence lies in its ability to enter human cells, primarily through interaction with the angiotensin-converting enzyme 2 (ACE2) receptor. This article discusses the mechanism by which SARS-CoV-2 exploits this gateway into human cells.
The ACE2 receptor is a protein on the surface of many cell types, including cells in the heart, kidneys, and lungs. It plays a crucial role in the body's renin-angiotensin system, which regulates blood pressure and fluid balance.
However, for SARS-CoV-2, the ACE2 receptor serves a different purpose: it acts as the entry point into human cells. Studies have shown that SARS-CoV-2 uses the same receptor for host cell entry as SARS-CoV, the virus that caused the SARS outbreak in 2003.
The process begins when the spike protein on the surface of the SARS-CoV-2 virus binds to the ACE2 receptor on a human cell. The spike protein has two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain (RBD) that recognizes and binds to the ACE2 receptor.
Once the RBD of the S1 subunit binds to the ACE2 receptor, it undergoes a structural change that allows the S2 subunit to facilitate fusion of the viral and cellular membranes. This fusion allows the viral genome to enter the human cell, where it hijacks the cell's machinery to replicate and produce more virus particles.
In addition, the spike protein requires priming by a host protease, an enzyme that cleaves proteins, to enable cell entry. The protease TMPRSS2 is thought to perform this priming function in lung cells. It cleaves the spike protein at specific sites, allowing membrane fusion and viral entry to occur.
Understanding the mechanism by which SARS-CoV-2 enters human cells via the ACE2 receptor has important implications for treatment and prevention strategies. Therapies could be developed to block the interaction between the spike protein and ACE2 receptor, preventing the virus from entering cells. Other strategies could target the protease TMPRSS2 to inhibit spike protein priming.