COVID – 19

Original hand drawn diagram of COVID – 19

Features of COVID-19

COVID 19, more commonly known when referring to the actual virus itself as SARS COV 2, is made up of many different parts, which are clearly labelled in the diagram above. However, here is a list of some of its features:

Size – SARS COV 2 has a typical diameter of 120nm, whereby 1cm is equal to 10000000nm. It really is very small.

Bilipid layer Envelope – The outer edge of a virus, responsible for holding the S proteins to gain access into a host cell, in order to reproduce. Also, it keeps all the parts of the virus together, preventing its RNA from escaping.

Spike (S) Glycoprotein – The S protein gives the virus its corona appearance, which gave the virus its name. Besides this, the S proteins are responsible for virus-cell membrane fusion, in order for the virus to infect the host cell for reproduction to multiply and grow in numbers.

E-protein – An e protein is essential on the surface of the virus for so many reasons, especially in the life cycle of the virus, such as assembly, budding, envelope formation and pathogenesis.

M-protein – The M protein is the most abundant protein on the envelope and it is responsible for the shaping of the envelope, while interacting with the other proteins in the envelope to take over the Golgi apparatus and the endoplasmic reticulum in the host cell.

HE – Hemagglutinin is responsible mainly for attaching to the outside of host cells to allow the S proteins to penetrate the membrane and infect the cell.

RNA and N protein – They contain all the genetic information of the virus, allowing it to invade the ribosomes and carry out protein synthesis to allow the virus to reproduce, and multiply in numbers.

Why Does Soap Work So Well?

Soap works very well against the COVID molecule because of COVID’s one obvious and prevalent weakness, the lipid bilayer on the envelope. The soap contains amphiphiles, which are lipids that are very similar to those on the envelope of the virus. Therefore, these lipids compete with the lipids in the viral envelope and breaking the non covalent bonds connecting them apart, dissolving the membrane and collapsing the virus molecule. Not only this, but the non covalent bonds between proteins and RNA are also broken apart and competed by the soap molecules. All together, the soap molecules outcompete and break apart the non covalent bonds in the virus, destroying it completely and preventing it from functioning.

How Do Alcohol Hand Sanitisers Work?

It is important to note that not all hand sanitisers work to destroy COVID 19, with only hand sanitisers with over 60% alcohol having any effect at all. However, for the ones that do contain this level of alcohol, the effect is similar to that of soap. While water is not lipophilic, alcohol is and so even though it does not form hydrogen bonds, it acts as a solvent and dissolves the lipid bilayer, collapsing the virus and disrupting any activities inside the virus, effectively destroying it.

How Does COVID-19 Infect Host Cells?

As aforementioned, the proteins on the envelope on the virus play a huge part in infection, especially the S proteins. On the cell membranes of respiratory cells, there are ACE2 receptor proteins, which are essential for normal bodily functions. However, these are the receptors that will prove fatal for the cell if it comes into contact with the deadly SARS COV 2 molecule. There is a clear method to the viral takeover:

  1. The S protein approached the ACE2 receptor and binds to it, connecting the virus to the host cell.
  2. More and more S proteins bind with more and more ACE2 receptors on the cell membrane on the host cell.
  3. This causes the cell membrane of the host cell to begin to bend and form around the SARS COV 2 molecule.
  4. A cell membrane forms around the SARS COV 2 molecule, which will grant access for the virus to access the cell.
  5. The newly formed cell membrane is able to fuse with the cell membrane of the host cell and the virus enters the cell.
  6. The virus’s other proteins on the envelope help to corrupt the Golgi apparatus and the endoplasmic reticulum, gaining control over the ribosomes and thus protein synthesis.
  7. The virus has found its host and the RNA and N proteins can undergo protein synthesis for the virus’ intended functions.

How Does The Immune System Deal With Viruses?

The problem with a virus is that it is not living as it cannot fulfil all of life’s processes and therefore needs to infect a host cell and use that to multiply. However, this makes it even more difficult for the immune system as it is impossible to differentiate between a healthy or infected cell, or is it?

Actually, cells have a system where they can actually show what is inside them using MHC Class 1 proteins, which are marker like compounds, which exist on the outside of cells, containing protein remnants of whatever is inside them. Therefore, infected cells will inevitably have remnants of the virus proteins on the outside of the cell, which is able to alert the immune system that there is a problem. However, the immune system needs to be able to find out which cells are infected; it is not controlled by hormones or nerves.

This is the job of T cells, namely the cytotoxic T cells, which roam the body in search of these peptides of viruses on the outside of infected cells. These T cells have special receptors on their surface called TCR’s which can detect specific antigenic peptides bound to the MHCs of cells, showing that they are infected. Now, the T cell is alerted of this and releases cytotoxic factors into the cell, killing it along with destroying the virus, preventing its spread. However, as seen before, this is not the end of the story, with viruses constantly mutating, a new problem can arise whereby the virus can stop the MHC protein from getting to the cell’s surface, making it impossible to be detected as infected. However, this is easily countered by natural killer cells, which can detect cells with a reduced number of MHC proteins on them, to which the release toxic substances to kill the infected cell, stopping the spread of the virus.

However, a situation may arise whereby a virus may be inside the system but may not yet have infected any cells, which requires another type of response involving B cells and phagocytes. The primary non specific response is phagocytosis, whereby the phagocyte, upon noticing the foreign particle, attempts to engulf and destroy it. However, sometimes, a more advanced or severe virus will overcome this first line of defence, meaning that a second line of defence is needed, which is more adaptive:

B cells roam the body’s blood, with the special capability of telling friend from foe or being able to recognise antigens and to not attack healthy somatic cells, with 10000 special receptors on their membrane, with each B cells being specific to one antigen. The more B cells we have, the higher the chance we can find a match. Once this match is made, the B cell binds to it and quickly reproduces, creating lots os B cells with the ability to create specific antibodies for this virus. Some of these are effector B cells, who just create antibodies, while others are memory B cell, responsible for remembering the specific antibody for the antigen for a quicker and stronger response next time. These antibodies can do a number of things:

  1. Neutralisation – The antibodies form a boundary around the virus, preventing its S proteins from locking onto any cells, rendering it useless until a phagocyte comes and destroys it.
  2. Agglutination – The antibodies link multiple virus cells together making it harder for them to move around the body and making it easier for phagocytes to engulf them.
  3. Marking – The antibodies mark the virus for destruction and also call in phagocytes.

Now, the phagocytes can come along and engulf the harmless virus, destroying it.

Vaccine for COVID-19

Before looking at the progress made into engineering a vaccine for COVID-19, it is important to recognise why a vaccine is needed in the 1st place. Actually, a vaccine keys in with the B cells mentioned above. When a vaccine is injected into the human body, harmless or inactive versions of the virus it is meant to immunise for are let into the blood stream, allowing the immune system to attack it. In this process, the B cells are able to find the specific antibody needed for the antigen, which means that memory B cells can remember this antibody. Now, the next time, when the actual virus enters the body in an uncontrolled fashion, it means a faster and a stronger response can be put into effect, destroying the virus before it can cause any harm. An ideal vaccine can do all of these thing but must also have the following properties:

  1. Safe for use
  2. High efficacy (achieving the desired effect)
  3. Low cost
  4. Easy administration
  5. Thermal stability
  6. Multivalency
  7. Long lived immunity
  8. High effectivity

Now we can see that a vaccine is very important on the road to immunising the population to a deadly disease, we must be aware of the progress made finding a vaccine for COVID-19. Right now (28/05/2020), there appears to be around 70 proclaimed vaccines that are being tested in the world, with varying amounts of success. However, it is important that the vaccines are tested properly first; if we inject a vaccine into most people in the world, only to find it causes infertility, we will have an even bigger problem. Therefore, it requires huge investment and efficient human and preclinical trials to try to quickly come up with an appropriate vaccine. This will take around 12 to 18 months, to ensure safety, but there are concerns around the issue of the virus mutating, causing a potentially more harmful strand of coronavirus to begin infecting the population, which may require another vaccine. However, it is also a major concern that a vaccine for this SARS COV 2 may never be found, and we may have to rely on natural mutations to make it as harmful as the common cold.

When testing a vaccine, there are significant ethical issues that arise. During a time of crisis like the time now, it is the moral obligation of the government and non governmental organisations to quickly provide incentives to develop a vaccine. However, like with all medical testing, we cannot know exactly how a human will react to a vaccine without trying it on a human. While animal testing and computer simulations provide some information regarding toxicity and some level of dosage, it requires human trials to see what effect will occur. Therefore, there is always a concern that the vaccine may cause harm to the human when testing, and because we are testing, there is no guarantee that this won’t happen. This is why there are often economic incentives to volunteer in the testing process. Even so, the issue of consent is important. The decision will always be in the volunteer’s hands.

How Does Testing Work?

There is a clear way that the COVID-19 rapid test kits work:

  1. A swab is taken from a patient’s nose or back of the throat and the sample is sent to a lab for analysis.
  2. RNA if the virus is extracted and purified, and an enzyme turns the RNA into DNA.
  3. Now, three things are added to the virus DNA: primers (parts of DNA that only bind with virus DNA), nucleotides and a DNA building enzyme.
  4. Repeated heating and cooing in a PRC machine means that the primers can bind with the virus DNA, while allowing the DNA building enzyme to copy the DNA strand millions of times.
  5. Fluorescent dyes are added to the DNA, which will only bind to the copied DNA, boosting their light emmitance.
  6. If there are lots of virus DNA in the mixture, then the mixture will be more fluorescent. Therefore, it it reaches a certain level, the test is considered positive.

However, the test is not 100% accurate, with there being double positive tests and double negative tests. Nevertheless, the test is a magnificent and significant tool in trying to limit the spread of COVID-19 before a vaccine is ready.

Bibliography

https://www.azuravesta.com/covid-19-pandemic

https://www.nationalgeographic.co.uk/science-and-technology/2020/02/heres-what-coronavirus-does-body/amp?__twitter_impression=true

https://www.pptaglobal.org/media-and-information/ppta-statements/1055-2019-novel-coronavirus-2019-ncov-and-plasma-protein-therapies

https://www.hayfestival.com/p-16788-daniel-davis.aspx

https://virologydownunder.com/why-does-soap-work-so-well-on-sars-cov-2/

https://micro.magnet.fsu.edu/cells/virus.html

https://www.sinobiological.com/research/virus/hcov-spike-protein-overview

https://virologyj.biomedcentral.com/articles/10.1186/s12985-019-1182-0

https://www.sciencedirect.com/topics/medicine-and-dentistry/virus-hemagglutinin

https://www.prevention.com/health/a31225112/does-hand-sanitizer-kill-coronavirus/

Coronaviruses – a general introduction

How do the tests for coronavirus work?

https://www.livescience.com/how-coronavirus-infects-cells.html

https://glycopedia.eu/e-chapters/Human-Immunodeficiency-Virus-the/The-mechanism-of-HIV-entry-to-the

https://www.immunology.org/public-information/bitesized-immunology/pathogens-and-disease/immune-responses-viruses

https://www.rndsystems.com/research-area/b-cells

https://pubmed.ncbi.nlm.nih.gov/24424920/

https://www.who.int/bulletin/volumes/91/4/12-113480/en/

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