The novel coronavirus SARS-CoV-2 is responsible for the outbreak of respiratory illness now referred to as COVID-19. The coronavirus particle (virus) is approximately 125 nanometers (nm) in diameter and is enveloped in a membrane. The viral envelope is studded with proteins, called spikes, that protrude about 20 nm from the surface of the virus. It is the interaction of these spikes with human cells that allows the virus to infect us.
The coronavirus spike is shaped like a horseshoe and is composed of two subunits, S1 and S2, that are connected at the base. The S1 subunit is responsible for binding the spike to a receptor on the human cell surface, while the S2 subunit is responsible for mediating viral membrane fusion with the human cell membrane. The receptor that the coronavirus spike binds to on human cells is called ACE2.
The amino acid sequence of the coronavirus spike is well conserved across different strains of the virus. However, the S1 subunit is the most variable region of the spike and it is this region that is responsible for binding to the ACE2 receptor. The coronavirus has evolved to bind to the ACE2 receptor with high affinity, which allows it to infect human cells efficiently.
The coronavirus spike is able to bind to the ACE2 receptor because it contains a binding domain that is similar in structure to a domain found in the ACE2 protein. When the coronavirus spike binds to ACE2, it induces a conformational change in the ACE2 protein that brings the ACE2 binding domain into close proximity with another region of the protein, called the catalytic domain. This proximity facilitates the transfer of a small molecule, called a protease, from the coronavirus spike to the ACE2 protein.
The protease that is transferred from the coronavirus spike to ACE2 is responsible for cleaving the protein into two parts, the N-terminal domain and the C-terminal domain. The N-terminal domain remains attached to the cell surface, while the C-terminal domain is free to enter the cell.
Once inside the cell, the C-terminal domain of ACE2 interacts with a protein called angiotensin-converting enzyme (ACE). This interaction inhibits the activity of ACE, which has a number of important functions in the body, including regulating blood pressure. The inhibition of ACE by the C-terminal domain of ACE2 leads to a decrease in blood pressure, which is thought to be one of the mechanisms by which the coronavirus causes illness in humans.
The coronavirus SARS-CoV-2 has evolved to efficiently bind to and infect human cells through the interaction of its spike protein with the human cell surface receptor ACE2. This interaction leads to the cleavage of ACE2 and the inhibition of ACE, which results in a decrease in blood pressure. The coronavirus SARS-CoV-2 is thus able to infect human cells and cause illness through a number of different mechanisms.
The way in which viruses and human cells interact is of vital importance in understanding how diseases develop. The current pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has shed light on how this particular virus uses human cells to cause disease.
SARS-CoV-2 is a positive-sense single-stranded RNA virus that encodes its genome within a protein capsid. The capsid is relatively simple, consisting of just two proteins, called spike (S) and envelope (E). The S protein is responsible for the attachment of the virus to human cells, and the E protein helps to protect the viral genome as it moves from one cell to another.
Once the virus has attached to a human cell, it begins to inject its genome into the cell. The viral genome then takes over the cell’s own machinery to begin replicating itself. This process is known as viral entry.
Viral entry is a complex process, and it is not fully understood how SARS-CoV-2 enters human cells. However, it is thought to use a combination of proteins to attach to and then fuse with the cell membrane.
Once the viral genome is inside the cell, it begins to direct the cell to produce more copies of the virus. The cell produces new virions, which then buds off from the cell surface. This process is known as viral replication.
Viral replication is a complex process, and it is not fully understood how SARS-CoV-2 replicates itself. However, it is thought to use a combination of enzymes to synthesize new viral RNA and proteins.
The new virions are then released from the cell, and the cycle begins anew. This process can lead to the rapid spread of the virus through a population.
SARS-CoV-2 is a novel virus, and scientists are still learning about how it causes disease. However, the current understanding is that the virus uses human cells to replicate itself and cause disease.
