Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as Covid-19, typically enters the body through the mouth or nose, after which the virus is transported to the lung’s alveoli (air sacs). The alveoli are responsible for oxygen and carbon dioxide exchange.
Modus of Infection and Replication
Once in the alveoli, the viral membrane spike glycoproteins allow the virus to penetrate the host cell.The spike glycoproteins, situated on the surface of the virion, attach to the host cell surface receptor, called the angiotensin-converting enzyme 2 (ACE2) receptor.
The transmembrane protease serine 2 enzyme (TMPRSS2) assists the virion to enter the host cell, after which the virion RNA is released into the host cell. Some of the RNA is translated into proteins by the host cell’s machinery, while others are replicated to form new viral RNA. Newly formed proteins and RNA are assembled in the Golgi apparatus to from new virions. The Golgi apparatus is specifically responsible for transporting, modifying, and packaging proteins and lipids into membrane-bound vesicles for delivery to targeted destinations. Once the virus’ RNA has entered a cell, new copies are made and the host cell is killed in the process, releasing new viruses to infect neighboring cells in the alveolus (multiple alveoli).
1. Spike protein on the virion binds to the cell-surface protein ACE2. The TMPRSS2 enzyme assists the virion to enter the host cell.
2. The virion releases its RNA
3. Some of the RNA is translated into proteins by the host cell’s machinery
4. Some of these proteins form a replication complex to produce more RNA
5. Proteins and RNA are assembled to form a new virion. This process takes place in the Golgi of the host cell.
6. The virion is released from the cell
The process of hijacking cells to reproduce causes inflammation in the lungs, which may trigger an immune response. If this response becomes excessive, it is known as a cytokine storm. A cytokine storm revers to a severe immune reaction in which the body releases too many cytokines into the blood too quickly, consequently attacking its own cells and tissues. Cytokines play an important role in normal immune responses; however, large amounts can be life threatening leading to multiple organ failure. If enough alveoli collapse, acute respiratory distress syndrome (ARDS) can occur, requiring a patient to be placed on a ventilator for breathing assistance.
When considering mechanisms of protecting the body against the SARS-Cov-2 infection, the following strategies may be considered:
- Preventing viral infection by limiting the spike proteins from binding to the cellular surface of the host cell or by deactivating enzymes required during the initial stages of infection.
- Eliminating or decreasing the rate of virion replication within the host cell, i.e. preventing Covid-19 onset.