Life cycle of the coronavirus
By Alfred Sibanda T.
Take a maize cob and have a good look at it, how many kernels does it have? Well, it’s about 800. From a single maize plant, you will get two cobs in most plants and that is approximately 1600 kernels from a single plant. Go back in time a little, how many kernels were planted in order for this plant to grow and produce these 1600 kernels, well, just one isn’t it? One kernel can give us 1600 kernels, that sounds like a masterpiece of nature, we all would love it if there were even bigger maize cobs right? Well it turns out, that property of nature works both for and against us. Turns out, that is almost the same way in which viruses multiply, except, unlike maize, a virus won’t take 3 months to produce that much, it will take much less time, unlucky for us.
The molecule at the centre of this phenomenon is the nucleic acid, found in living organisms. The nucleic acid is responsible for storing all the information needed to make an entirely new organism from an existing one. As we discussed earlier, in humans, bacteria, protozoa and fungi, that material is Deoxyribonucleic Acid (DNA) whereas in viruses, it can either be DNA or Ribonucleic Acid (RNA). Coronaviruses are RNA viruses, which means they have all their information stored in the form of RNA.
Ribonucleic Acid viruses can either be single stranded or double stranded, segmented or non-segmented. Single stranded RNA viruses have just one strand of RNA and they make up most of the RNA viruses whereas double stranded RNA viruses have two strands of RNA, linked together in the form of a double helix, these are quite few in comparison to the single stranded counterparts. Non-segmented RNA viruses either have just a single RNA strand or a double stranded RNA helix whereas segmented RNA viruses have many separate strands carrying the information.
Coronaviruses are single stranded RNA viruses. Single stranded RNA viruses can either be positive sense or negative sense. The ‘sense’ description is terminology used to refer to whether the RNA of the virus can be immediately translated into proteins or not. Positive sense RNA viruses are those viruses whose RNA can be copied into proteins as soon as the virus enters a host cell whereas a negative sense RNA virus is one whose RNA cannot be immediately copied into viral proteins but rather needs to be first copied to make positive sense RNA before translation. In other words, positive sense RNA is that which has the same polarity as our own RNA and hence can be acted upon by our enzymes whereas negative sense RNA cannot be acted upon by our enzymes.
For details on how coronaviruses are transmitted from one person to another refer to the article on Transmission and prevention of covid-19. We now look at how the coronavirus enters and replicates within the host cell.
Respiratory viruses affect the upper and lower respiratory tracts but with different prevalences. The first part to be infected is usually the upper respiratory tract where the virus enters. In most cases, in an individual with a strong immune system (immunocompetent individual), the infection is dealt with while it is still in the upper portion of the respiratory tract, however, in individuals with weak immune systems (immunocompromised individual), the viruses often progress to infect the lower part of the respiratory tract which includes our vital organs, the lungs, and this leads to complications, often ending in death. Moreover, once the respiratory infection gets into the lower respiratory tract, it becomes easier/more likely for the patient to transmit it. This is because as the virus gets into the lower parts of the tract, it causes irritation of more of the respiratory surface and hence more coughing and production of fluid which can then be passed on to other people who are exposed to it. It has been found that coronaviruses tend to progress and infect the lower respiratory tract more often than most other respiratory viruses. When compared to the seasonal flu, the coronaviruses are more contagious as one person on average infects 2.2 people whereas with flu one person infects 1.3 people.
When the upper respiratory tract is infected, signs include shortness of breath, sore throat, dry cough, headache, fever and fatigue. Infection of the lower respiratory tract causes a severe productive cough, tightness of the chest, shortness of breath and wheezing. When the lower respiratory tract is infected, the body mounts an inflammatory response and this, as in many other cases, can exacerbate the symptoms. When the lungs or any part of the body is infected, blood flow to the organ increases and this is to increase the amount of immune cells reaching the area in order to fight off the infection. This increase in blood flow together with widening of blood vessels causes fluid from blood to leak into the lung, delivering the immune mediators but also causing a harmful accumulation of fluid in the lungs which eventually leads to the symptoms I mentioned above. At this point the patient needs assistance breathing and this is done using a ventilator. Studies have shown that women mount a greater response to viral infections and hence they tend to less frequently develop lower respiratory infections as compared to men. Additionally, women generally tend to seek medical attention earlier than men in most cultures.
The life cycle of a coronavirus once it enters the body follows the sequence: binding to the cost cell surface e –> entry in to the host cell –> uncoating –> translation of replicase proteins –> transcription of RNA –> synthesis of RNA –> virion assembly –> release of mature virion –> repeat of the cycle.
“Just one cough I was exposed to, just that one time I went into town and now I have the virus in my system and can actively spread it? But how? I think I was not exposed to a lot of virus particles, but now I’m suffering!” For those who find this unbelievable, here is the cycle of the virus and how we get so many from so few.
Our body is made up of cells, different kinds of cells depending on where they are located. Some of these differences lie in the types of protein molecules expressed on the cells. These protein molecules on the cell membranes perform different functions including enzymatic functions and cell signalling functions. Cells in the respiratory tract have a protein molecule called Angiotensin Converting Enzyme 2 receptor. This protein molecule so happens, as nature would have it, to be complementary to the surface proteins of the coronavirus SARS-CoV-2. This means that the virus binds to this protein very well, and this is the first step in the entry of the virus into the cell, the binding. It has been shown that the SARS coronavirus, a relative to the SARS-CoV-2 that is currently affecting us, in infected monkey kidney cells, begins to bind cells after about three hours of inoculation, we can use this as an estimate for what happens in humans infected with the SARS-CoV-2.
Next the envelope of the virus then fuses with the host cell and this aids entry as it then uncoats inside the cell, releasing its positive sense RNA strand into the cytoplasm of the host cell. This RNA encodes a replicase enzyme which is then translated from it, making a polyprotein that can be further cleave into individual replicase proteins. Replicase proteins do just that, they replicate, or copy the RNA, producing another strand of RNA, which has a negative sense. This means that it cannot be used to synthesize proteins by translation. This being the case, this negative sense strand serves as a template for production of more positive sense strands. Clever isn’t it?
Positive sense mRNA strands are then produced off this negative sense RNA, these encoding the structural and non-structural proteins of the virus.
Structural proteins of the virus include the envelope (E) proteins, spike (S) proteins, nucleocapsid (N) proteins and membrane (M) proteins. These together with non-structural proteins are then translocated into the Rough Endoplasmic Reticulum and the Golgi apparatus for processing after which they mature and bud off from the Golgi membrane as small vesicles, the vesicles are then moved to the cell surface membrane where they fuse and exit the cell. From a few viral particles entering a cell, we produce many more of them. What happens next? Well it doesn’t stop there, each of these then go on to infect other cells as well in the respiratory tract and as you can imagine, this time an even greater number of virions is going to come out of the infected cells, and on and on.
Fluid in the respiratory tract gets infected by these virus particles and it is these that can then be transmitted from an infected person to a second person, leading to another infectious cycle within the new victim. For our description of how these are transmitted from one person to another, take a look at the article on Transmission and prevention of COVID-19.
In order for us to contain the spread of the virus, there is need for collective efforts from all of us. We need to obey the regulations set by the World Health Organisation including social distancing, proper wearing of masks, regular handwashing with soap, reporting any suspected cases, avoiding unnecessary travel etc. Together we can bring down COVID-19!
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