SARS-CoV-2
COVID-19 codes for five specific proteins. The S-protein (spike) governs the tissue of the virus, is part of the outer structure, and improves host cell entry. The E-protein (envelope) alters the host secretory pathway, increases disease symptoms, and helps particles escape and release that has ion channel activity. The HE-protein (hemagglutinin) is on the outer structure of the cell and helps the S protein in improving host cell entry. The M-protein (membrane) exists on the outer structure, gives the virion shape, and is the most abundant that consists of three transmembrane domains. The N-protein (nucleocapsid) mainly organizes the viral genome. COVID-19 along with many other viruses can have both positive and negative sense RNA that includes replicase. The genetics of COVID-19 consist of 5’ and 3’ tails allowing it to act as mRNA for polyproteins, and replicase takes up two-thirds of the genome. This leads to determining that COVID-19 is an enveloped virus and contains positive sense RNA viruses. For the life cycle of COVID-19, the S-protein initiates the process by attaching to the receptor. This is mainly how the host becomes infected with this virus. Next the virus must next gain access to the host cell cytosol. This is accomplished by the cleavage of S protein by a cathepsin, TMPRRS2 or another protease. The next step in the coronavirus lifecycle is the translation of the replicase gene from RNA. Following replication and sub-genomic RNA synthesis, the viral structural proteins, S, E, and M are translated and inserted into the endoplasmic reticulum. The M protein then directs assembly of the coronavirus.
Angiotensin is the main molecule that SARS-CoV-2 attaches to. However, the pairing for the principal virus molecule cell attachment is Angiotensin (ACE2) and Spike. This molecule is responsible for increasing blood vessel diameter and enzymatically cleaves angiotensin and is mostly classified as a converting enzyme. Outer structures of the body express ACE2, and these are typically the heart, lungs, kidney, artery, and intestines. ACE2 also serves as the entry point for some coronaviruses and is used as the receptor. SARS-CoV-2 is assembled in the Plasma membrane and Extracellular matrix with mitochondrion, lysosome, peroxisome, and cytoskeleton acting as the secondary binding molecule along with the primary molecule. For the viral structure proteins, Spike, Membrane, and the Envelope are assembled in the endomembrane secretory pathway. As for the viral genomic components such as RNA and nucleocapsid, they assemble in the cytoplasm. (Fehr and Perlman, 2020) Unfortunately, though, scientists and researches do not quite understand where the structural and genomic components of the virions assemble, nor do we understand how the virus interacts with proteins inside the cell.
The tissues that are primarily responsible for binding to SARS-Cov-2 are the brain, lungs, heart, smooth muscles, kidneys, intestine, and blood vessels. (Goor, 2004) This corresponds to the reported symptoms because most people are experiencing symptoms such as headache, coughing, sneezing, respiratory pneumonia, blood pressure changes, etc. which would make since if most of these tissues are being affected by primary binding. For the assembled virions to get out of the host cell they are transported to the cell surface and then shed tons of virions via exocytosis. However, it is not currently known if the virions use a traditional pathway for transport or if the virus has created a unique, separate pathway to contribute to its own exit. Some weird symptoms that have came to light since COVID-19 are lack of taste, lack of smell, foot sores, “fizzing”, and pink eye. Some of these symptoms are extremely possible, such as lack of smell and taste. It is common for that when a person is sick, they tend to lose a sense of smell or lack particular taste buds. This is why when people are ill they often experience bad food that usually tastes good, or bad smells, that someone tends to like, and vice versa. However, a symptom of “fizzing” could be less likely. It has been reported that “fizzing” is the sensation of buzzing throughout the body. Though doctors have said this is very rare and unlikely, they have said it could be possible if a person is experiencing an autoimmune response to the immune system.
This virus gets into the cell once it has been bound by endocytosis. It is also known that the cell enters through direct fusion with the plasma membrane. The virus then has interaction with ACE2 and Spike as a primary molecule to secure its way in or it has help from Sialic Acid and Hemaglutinin as a secondary binding molecule source. Scientists believe some sort of Clathrin dependent and independent pathways play as well as macropinocytosis a role in this as it has been reported, but researchers say they are still looking for more information. When the virus is engulfed in the cell, it is mainly mediated by the endocytic pathway. With this being said, lysosomes play an important factor and are the main source of degradation for this virus.
Lastly, as believed by scientists, structural and genomic components of SARS-CoV-2 have come together by natural origin and processes. It is also reiterated that the spike proteins exist on the outside of the cell, which leads to the main penetration of the virus in the human cells. This is also benefited by the help of ACE2 and the envelope. (Anderson, 2020) Since this is a new form of the original SARS-CoV, it has a similar structure of where each protein and component lies on the virion, however, new coronavirus information is being discovered every-day, and it will probably take a few more months to discover how each genomic and structural component intertwine and interact with each other.
References
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H (June 2004). “Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis”. The Journal of Pathology. 203 (2): 631–7.
Kristin G. Anderson (2020). “The proximal origin of SARS-CoV-2.” Nature Medicine
Fehr R, Anthony, Perlman, Stanley (2020). “Coronavirus: An Overview of their Replication and Pathogenesis” Methods Mol Bio.