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Morphological Analysis Of SARS-CoV-2 | Genome Organization | Replication | Pathogenesis (SARS-CoV-2) | Wit Biology

                       Morphological Analysis Of SARS-CoV-2 

        We will be taking a look in this article at the structure of the corona virus responsible for the current pandemic and how its structure causes its clinical manifestation. Coronaviruses are a large family of common viruses which are found in humans and animals many cases of the common cold are due to a corona virus. 

        They have caused two large-scale outbreaks in the past two decades the SARS virus in 2002 and the MERS virus in 2012. It's generally been considered that these corona viruses could cause future disease outbreaks. Because they're known to be able to evolve within animals and then jump to humans fire an intermediate host in SARS palm civets and raccoon dogs were identified as the intermediate covid-19 is an example of this which is believed to have jumped from bats to pangolins to humans in a local seafood market in Wuhan China during 2019.

       Covid-19 refers to the corona virus infectious disease found in 2019 the actual disease itself is referred to as covid-19. But the virus is called the SARS cough - which stands for severe acute respiratory syndrome coronavirus - and was named because its structure very closely resembles that of the SARS virus from 2002. This is the seventh known corona virus to infect humans two of which were similarly highly pathogenic MERS and SARS. The other four are of low pathogenicity and endemic in humans. 

       Let's now take a look at the structure of the SARS cough - virus so looking at this virus we can see that it has a series of protein spikes on its surface which when viewed under a microscope appear like a crown which gives rise to the name corona. Which is Latin for Crown and is therefore common to all the corona viruses. 

       There are four structural proteins which is similar to other corona viruses the S the E the M and the N proteins. 

  1. The S stands for spike. 
  2. The E stands for envelope. 
  3. The M stands for membrane and 
  4. The N stands for nucleo capsid. 

       So let's take a look at these different structural proteins in turn beginning with this crown-like structure which is the S or spike protein this protein is responsible for allowing the virus to attach to the membrane of the host cell. It contains a receptor binding domain which recognizes a specific receptor the angiotensin converting enzyme receptor 2 which is expressed in their lungs heart kidneys and intestines it has been shown that this protein binds to the ACE 2 receptor with at least the same affinity and potentially as much as 20 times greater affinity than the SARS virus this could be one of the explanations for the reasons, why it's spreading so easily the spike protein itself has two functional subunits s1 binds to the host cell receptor and s2 mediates the fusion of the viral and cellular membranes, because of the critical role that protein plays in binding to target cells and cellular entry. It is a particular focus in the design of vaccinations and medical treatments for covid-19. 

        Let's take a look at the next protein the M or membrane protein. The membrane protein is the most abundant on the viral surface and defines the shape of the viral envelope. It can be thought of as the central organizer for corona virus assembly and interacts with the other structural proteins. 

        Moving on to the E or envelope protein. This is the smallest of the major structural proteins on the viable membrane. Which appears to have several roles we know that it is integral in the assembly and release of the virus from host cells and during viral replication it is largely localized at the site of intracellular trafficking more specifically at the endoplasmic reticulum and the Golgi apparatus so essentially the M and E proteins play a critical role in turning the host cell apparatus into workshops where the virus and our own cells work together to make new viral particles underneath the surface proteins.We have the viral envelope. This is the viruses out that is derived from the hosts cell membrane so ourselves or the animals it's a fatty layer and worth noting that in contact with soap it will break down killing the virus and this is the reason why hand-washing with soap is so important to prevent the spread of this virus underneath this layer is what's called the capsid this is a protein shell that encloses the genetic material of the virus inside this capsid. 

        We have the nuclear capsid or N protein. This protein is bound to the virus's single strand of RNA which is where all its Dometic information is held to allow itself to replicate the N protein appears to be multifunctional in particular it essentially inhibits a lot of the host cells defense mechanisms and assists the viral RNA in replicating itself and therefore in creating new viral particles. 

       So we've looked now at some of the important structural features of the SARS coronavirus to a lot of our understanding of the pathogenesis of covid-19 comes from work on the original SARS virus. The costly viral structures in morphology are so similar there is likely to be significant crossover in the biochemical interactions and pathogenesis. 

       Let's now look a little more at how the virus infects humans. So the virus is spread mainly by respiratory droplets ie a cough or sneeze which aerosol is the virus allowing it to travel into our nasal or all cavities. We also know that it can live on surfaces for hours and even up to a few days on some surfaces so if you touch an infected surface it's very easy to then touch your own face and to knock you late the mucous membranes in your eyes mouth or nose with the virus initially it can get into the upper airway, so the nasal or throat area and this is why you can get those symptoms like a common cold, stuffy nose, headache, sore throat and fever. It is within the mucosal epithelium of the upper GI tract where primary viral replication is thought to occur similar to SARS. SARS coronavirus to is able to get further into our respiratory system and into our lung epithelial cells we're further viable that location occurs. 

       Let's talk a little bit more about the ACE to receptor interaction the SARS coronavirus 2 binds violet spike or S protein to the ACE 2 receptor, this mechanism of binding is the same way that the SARS virus was able to bind to airway epithelial cells. The host cell has proteases which are enzymes that break down proteins and these cleave the spike protein we think that this process activates the protein in order to trigger the process of membrane fusion, before injecting the viral genome into the host cell a similar mechanism of protein cleaving facilitates. 

       Cell entry in influenza as well as this mechanism of direct cellular entry the virus may also enter the cell via endocytosis. This is the process by which material enters a cell after being surrounded by an area of the cell membrane which then buds off inside the cell to form a vesicle once inside the cell fire a specific RNA and proteins are synthesized within the cytoplasm further viral proteins are then assembled with the blueprint of information contained within the viral RNA using the hosts cellular machinery specifically the endoplasmic reticulum and Golgi apparatus with specific processes to form the envelope glycoproteins new variants are then assembled by fusing to the plasma membranes and released as vesicles via the cellular EXO CITIC secretory processes. So the stress is placed on our own cells by viral infection and the interaction of our own immune system with the viral antigens presented by the infected host cells lead to cell death during this process of cell death. Multiple inflammatory mediators are released which creates an inflammatory response leading to a buildup of mucus and thickening and hyperplasia of the cells within our Airways this inflammation causes irritation of the cells lining our Airways which leads to the cough. 

          Let's move further down into the lower respiratory tract now and see how the virus acts within the lungs. So let's take a look at the path that the virus might take, so looking at the track here are the windpipe this branch is into left and right main bronchi. These bronchi branch into lobar bronchi we have three on the right and two on the left and these then branch into segmental bronchi. The segmental bronchi branch into bronchial which terminate as respiratory bronchioles at the end of which are the alveoli the alveoli are the tiny air filled pockets responsible for gas exchange. We have around 600 million of these alveoli and they are responsible for exchanging oxygen and carbon dioxide between the blood and the air we breathe in due to the direct action of the virus and also due to our own immune systems response to viral infection the alveolar walls can become inflamed and thickened and fill the alveolus with fluid, which can impair their ability to exchange gases and this can lead to the symptom of shortness of breath in some people this process of cellular infection by the SARS cough - virus can lead to an exaggerated immune response with a huge release of pro-inflammatory mediators causing what is known as a cytokine storm or cytokine release syndrome

         Cytokines are small proteins involved in cell signaling and are crucial in mediating immune responses this cascade of inflammatory mediators causes an uncontrolled systemic inflammatory response, which leads to acute respiratory distress syndrome or a RDS. This is the rapid and widespread inflammation in the lungs which causes the epithelial and endothelial cells of the lungs to secrete inflammatory mediators which fill the alveoli in addition these inflammatory signaling cells recruit other cells of the immune system into the alveoli, which further contributes to and amplifies the problem further the systemic inflammatory state causes increased capillary permeability which results in even more fluid entering the alveoli. So essentially this is non cardiogenic pulmonary edema compounding the problem over all this pathological process severely impairs the ability of the lungs to exchange oxygen and carbon dioxide as it's now become filled with fluid and inflammatory infiltrate in cases of severe a RDS invasive mechanical ventilation is required to adequately oxygenate the body. 

        So that's what underpins the pathology at the extreme end of the spectrum in the large majority of cases of covid-19 infection the disease follows a mild course as the viruses eliminated via normal immune processes. on CT as seen on these axial and coronal slices typical findings are lower lobe predominant bilateral subfloor ground glass density opacities while these findings are frequently seen in covid positive patients. These are not specific the differential for these appearances includes other viral pneumonias interstitial lung diseases such as cryptogenic organizing pneumonia and atypical bacterial pneumonias so that completes this article with some covid-19 pictures. ❤️✌️... 

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