SARS-COV-2 Kayla Marciniak
Viruses can have genomes that are composed of DNA or RNA, and they can also be single or double stranded. The SARS-COV-2 virus has a positive -sense RNA genetic makeup. Positive strand RNA have the coded information about how to build proteins in their genetic makeup, whereas negative strand RNA have the opposite. Negative strands have to be transcribed into positive strands before they can be used by the host. RNA can be replicated faster than DNA and is highly mutatable. This can enable a viral infection to grow rapidly and be resistant to medications if it mutates often. The SARS-COV-2 virus codes for four proteins- spike (S), envelope (E), membrane (M), and nucleocapsid (N). The S protein helps the virus attach to the host cell, the E protein helps protect and release the virus, the M protein helps keep the virus’ shape, and the N protein helps keep the genetic material contained. This virus is enveloped, which means that it is encased in a lipid bilayer membrane, unlike non-enveloped viruses that are only enclosed with the capsid layer (Fehr and Perlman, 2015). Enveloped viruses are often more sensitive to things like pH, temperature, and chemicals used to disinfect surfaces. However, the envelope is derived from host cells, so it makes the virus harder for the host’s immune system to recognize it (Wikipedia 2020).
The SARS-COV-2 uses the spike (S) protein to attach to a host cell’s membrane. This club-shaped protein has two parts – S1, which makes up the tip where it binds to a cell receptor, and S2, which makes up the stalk. It is also glycosylated and contains a trimeric S-glycoprotein that helps facilitate the protein’s attachment to a recepto (Fehr and Perlman, 2015). The virus enters a cell by way of receptor-mediated endocytosis or membrane fusion. In humans, the S protein attaches to angiotensin-converting enzyme 2, or ACE2. ACE2 normally lowers blood pressure by hydrolyzing angiotensin II, which is a vasoconstrictor, into angiotensin (1-7), a vasodilator. ACE2 is found in many human cells, including the intestines, arteries, veins, kidneys, brain, and heart. However, ACE2 is mainly found in alveolar cells in the lungs. Once the receptors are bound together, the virus and the enzyme’s membranes fuse and both are put into endosomes. Serine 2 (TMPRRS2, [or another protease]) helps to facilitate the fusion. When the S protein fuses with the receptor on a host cell, it also determines the virus’ tissue tropism – it helps the virus figure out which cells it can infect and will support its growth (Wikipedia 2020).
The next step is replication. The virus must translate its replicase gene from its RNA to be able to form more virions. Many non-structural proteins are needed to ensure that RNA synthesis is able to occur. These nsps are also integral to the replication and transcription of the RNA . Some nsps are also involved in other important tasks, such as blocking the immune system responses to viral activity (Fehr and Perlman, 2015). Once the replication and transcription are complete, translation and assembly follows. RNA is synthesized, and the structural proteins are translated. Once the S, E, and M proteins are translated, they are put into the endoplasmic reticulum. These proteins are then transported along the secretory pathway to the ERGIC, or the endoplasmic reticulum-golgi intermediate compartment. N-encapsidated viral genomes are then added to the compartment that contains the structural proteins, M binds to the nucleocapsid and a full virion is complete (Fehr and Perlman, 2015).
Virions are moved from the ERGIC to the cell membrane by transport vesicles. Scientists are still unsure if the virus itself facilitates a specific route to the cell membrane or if it uses a route the host cell already has in place. Once the vesicle reaches the cell membrane, it is released by exocytosis. In some instances, the S protein of the virus that was not included in a virion can travel to the host cell membrane. There, it can facilitate fusion of cell membranes with non-infected and infected host cells, creating large infected host cells. This could allow the virus to continue to replicate without being destroyed by the host’s immune system (Fehr and Perlman, 2015).
Given the cells that SARS-COV-2 can bind to, it is reasonable that the majority of symptoms are confined to the upper-respiratory system. While there are other symptoms such as gastrointestinal upset, muscle aches, and chills associated with the virus, the most reported are coughing and difficulty breathing. This coincides with what we have learned about the virus and its attachment to the ACE2 receptors in the epithelial cells in alveoli of the lungs. However, one symptom that stood out was disorientation (CDC, 2020). Of course, any imbalance or infection could potentially have effects on the brain, but this particular virus generally targets epithelial tissue. There is some epithelial tissue in the brain, but not nearly as much as the lungs contain, which makes the disorientation an interesting symptom. I do believe this symptom is legitimate. One could contribute the disorientation to a high fever, since neurologic function is vulnerable to prolonged periods with a fever over 101.3 degrees Fahrenheit (Walter and Carraretto, 2016). Even with the information we studied, this virus is ever-evolving and is a serious threat to public health and should be treated as such. The more we learn about it, the better prepared we will be if it causes another outbreak.
(1) 2020. Severe acute respiratory syndrome coronavirus 2. (Wikipedia).
(2) Fehr, A., and Perlman, S. 2015. Coronaviruses: An overview of their replication and pathogenesis. HHS.
(3) Center for Disease Control (CDC), 2020. Coronavirus disease 2019. Situation Summary.
(4) Walter, E. J., and Carraretto, M. 2016. “The neurological and cognitive consequences of hyperthermia.” NCBI.