1. SARS-CoV-2? Covid-19? What are the key terms to know?
The COVID-19 pandemic is caused by a virus that’s called SARS-CoV-2. Let’s start by looking at what these acronyms stand for, as well as some associated terms.
- COVID-19 stands for Coronavirus Disease, 2019.
- Coronaviruses are a family of viruses that cause a variety of diseases. Some coronaviruses cause the common cold. Others, such MERS (Middle Eastern Respiratory Syndrome), cause much more serious diseases.
- SARS-CoV-2 stands for Severe Acute Respiratory Syndrome Coronavirus-2. According to Merriam Webster Online, the way to say the acronym is \ ˈsärz-kō-ˈvē-ˈtü \, with 4 syllables. It’s
- Severe because it can be a serious disease.
- Acute because it comes on suddenly (as opposed to a chronic condition that you live with for a long time).
- Respiratory because it involves tissues in the lungs.
- A syndrome because there’s an array of symptoms.
- “2” because it’s the second coronavirus of this type to cause a pandemic. The first was called SARS-CoV, and it caused a pandemic that occured in 2003 (one that was far smaller than the current COVID-19 pandemic.
How is a pandemic different from an epidemic? A pandemic is a disease that occurs in many countries or regions at the same time. The SARS outbreak of 2003 spread to 29 countries, affecting over 8000 people and resulting in 774 deaths (Source: CDC.gov). The current COVID-19 pandemic is much wider in scope. As of December, 2020, it has spread to 218 countries, affected 61.9 million people, and caused over 1.4 million deaths (source: NY Times)
Most disease outbreaks are epidemics. An epidemic occurs in just one region or country, or even one area within a country. For example, the Ebola virus outbreak that occurred between 2014 and 2016 was mostly confined to Western Africa, making it an epidemic.
2. How big is SARS-CoV-2, and why is that important?
Like all viruses, SARS-CoV-2 is incredibly small. If you’re looking at this on a laptop computer, then the image on your right is about 5 centimeters in diameter. The actual virus is 100 nm (nanometers) in diameter. A nanometer is a billionth of a meter, so that’s 500,000 times smaller than what you’re seeing. Some more useful comparisons might be:
- a DNA molecule is about 2 nm wide. A single viral particle of SARS-Cov-2 is about 50 times wider than DNA.
- According to The Engineering Toolbox, household dust is at least 50 nm in diameter, and could be up to 1000 times larger. So one viral particle is at most twice the size of a particle of household dust, and could be much smaller.
The comparison with dust is important. We’ve all seen dust floating in the air. If dust can float, then so can SARS-Cov-2. If you spend time close to someone who’s infected with SARS-Cov-2, then you might breathe in some of the viral particles that that person exhales. As we’ll see below, that can lead to you becoming infected.
3. What are the key structures in SARS-Cov-2?
SARS-Cov-2 is an RNA virus. That means that RNA (number 6 in the diagram at left) makes up its genetic material. To review RNA’s structure, click here.
The RNA that makes up the SARS-CoV-2 genome consists of about 30,000 nucleotide bases. These bases code for 11 genes, which are expressed as 12 proteins.
The RNA is enclosed and protected by nucleocapsid proteins (3, at left). The nucleocapsid proteins fit together to form a protective capsid (more easily seen in the image below from UK Research and Innovation).
In many viruses, such as the phage discussed in the previous tutorial, a genetic core and a capsid make up the entire structure of the virus. But in viruses that infect animals, there are often additional layers, and that’s also true of coronaviruses. In all coronaviruses, a lipid envelope (2) surrounds the nucleocapsid. This envelope is composed of a phospholipid bilayer, the same structure that makes up cell membranes. As we’ll see below, this phospholipid bilayer is “stolen” from the cells that the virus infects.
Embedded in the lipid envelope are several other proteins. The most prominent of these is the spike protein, at 1. These spikes create the corona (corona means “crown”) from which coronaviruses get their name. The spike protein is a quaternary protein, composed of 3 identical polypeptide subunits, one of which is shown in a highlighted, cartoon form in the diagram. As an AP Biology student, you should notice the many alpha helices that are part of the protein’s secondary structure, as well as the hairpin-turns that are part of tertiary protein structure.
The spike is important because it’s how the virus enters into cells. The cyan portion of the diagram (right at the top) is the receptor binding site. As we’ll see below, this part of the spike binds with a receptor on a cell in a person’s lungs, inducing that cell to absorb the virus.
Another reason why the spike protein is important is that it’s the target of SARS-CoV-2 vaccines.
Two other proteins embedded in the virus’s membrane are the M protein (also known as the membrane protein, shown at 4) and the E protein (also known as the envelope protein, shown at 5).
The image at right, from a 3-D model on “Getting to know the new coronavirus” by UK Research and Innovation, shows these structures in spectacular detail. Click the image to enlarge it.
- Spike protein
- phospholipid bilayer
- nucleocapsid protein
- Membrane protein
- Envelope protein
4. SARS-CoV-2 Structure: Checking Understanding
Before delving deeper, let’s check for understanding.
[qwiz style=”width: 600px !important; min-height: 400px !important;” qrecord_id=”sciencemusicvideosMeister1961-SARS-CoV-2 Structure” random=”true”]
[h] SARS-CoV-2 Structure: Checking Understanding
[q] In the diagram below, the spike protein is at
[q] In the diagram below, which part is made of phospholipids?
[q] In the diagram below, the nucleocapsid is at
[q] In the diagram below, the virus’s genetic material is shown at
[q] In the diagram below, which part is made of RNA?
[q] In the diagram below, the spike protein is at
[q] In the diagram below, RNA is shown at
[q] In the diagram below, the nucleocapsid is shown at
[q] In the diagram below, which part was stolen from internal and external membranes of the cell that was used to make the virus?
[q] The “A” in SARS stands for [hangman]
[q] A disease outbreak that occurs in many places at the same time is known as a [hangman]. By contrast, a disease the occurs in just one location is known as a(n) [hangman].
[q] In the reading above, you learned that a single SARS-CoV-2 particle is about 50 times wider than a molecule of [hangman], but much smaller than a particle of [hangman] floating in the air. And because the virus can float, it’s very important to protect yourself and others by wearing a [hangman].
[q]The spike protein is a [hangman]-level protein, consisting of 3 polypeptide chains.
In the image at left, you can see a few long alpha helices, which is a [hangman] protein strucure.
5. How does SARS-CoV-2 Infect Cells?
To get infected by SARS-CoV-2, you have to breathe it in. According to the U.S. CDC (Centers for Disease Control):
COVID-19 spreads between people who are in close contact (within about 6 feet) through respiratory droplets, created when someone talks, coughs or sneezes. Staying away from others helps stop the spread of COVID-19.
Once you breathe it in, the virus can come into contact with the cells in your respiratory system. As we’ve seen in the previous tutorial in this module, viruses take control of cells and convert them into virus factories. The image below shows how this works for SARS-CoV-2.
Suggestion: Keep the image in view as you scroll the text below.
- Steps 1 and 2: Viral binding and entry, Release of viral RNA.The infection cycle begins when the spike protein on SARS-CoV-2 binds with the ACE2 protein (at B) on the membrane (C) of an epithelial cell in the respiratory system. Epithelial cells form the outer lining of tissues in the nasal cavity, the lungs, and the blood vessels. “ACE2” stands for angiotensin-converting enzyme 2. ACE2’s function is to modify a hormone called angiotensin, which is used to regulate blood pressure. During the course of the evolution of SARS-CoV-2, its spike evolved in such a way that its shape became complementary to the shape of ACE2. That essentially made ACE2 into a receptor for SARS-CoV-2. Binding of the spike protein with ACE2 induces the cell to carry out something very similar to receptor-mediated-endocytosis. In this process, binding of a ligand with a receptor causes the cell membrane to buckle inward, bringing in whatever has bound to the receptor. The result, shown at 2, is that the RNA of SARS-CoV-2 is able to enter into its new host.
- Step 3: Synthesis of viral RNA polymerase. SARS-CoV-2 is what’s called a positive sense RNA virus. That means that its RNA can serve as messenger RNA for the ribosomes of an infected cell. One of these ribosomes is shown at “D.” Note that this ribosome “belongs” to the infected cell. If you were infected, it would be one of your ribosomes, in one of your epithelial cells.This ribosome reads the virus’s RNA message and makes a protein that’s unique to RNA viruses:RNA dependent RNA Polymerase, also known as RNA replicase (shown at “F”). RNA replicase uses RNA as a template to synthesize a complementary strand of RNA. Note that while only one RNA replicase is shown, many are synthesized.
- Step 4: Replication of Genomic RNA. When RNA replicase synthesizes new RNA, that new strand is synthesized as minus RNA: it’s the complement of the original positive strand. In step 4, RNA replicase uses the minus RNA as a template to synthesize complementary RNA (at “G”). That strand of RNA is a replica of the 30,000 base RNA that makes up the virus’s genetic material (its genome). Later, in step 8, that genomic RNA will be incorporated into a new virus particle.
- Step 5: Replication of Structural RNAs. The genome of all coronaviruses consists of a variety of structural genes that code for viral proteins, including the spike protein, nucleocapsid protein, and other proteins discussed above. In step 5, RNA replicase creates copies of the mRNA for each of these proteins. These mRNAs are shown at “H.”
- Step 6: Translation of viral proteins. In step 6, ribosomes (not shown) translate these viral mRNAs at “H” into viral proteins (shown at “J”). These proteins are inserted into the endoplasmic reticulum (at “I”).
- Steps 7 and 8: Budding of vesicles from the ER; creation of new viruses. In step 7, vesicles with viral proteins bud off from the ER. In the cytoplasm, these vesicles combine with genomic RNA. With all required parts present, new viruses (“L”) are assembled (step 8).
- Step 9: Exocytosis and release of new viral particles. The newly formed virus at “L” is encased in a vesicle. In step 9 that vesicle fuses with the cell’s membrane (at “C”). This releases new viruses from the cell (shown at “M”). This virus may go on to infect other cells within the same person, worsening the infection. Alternatively, all it takes is for the infected person to exhale, speak, sing, cough, or sneeze to move that virus (along with many others) outside of his or her body. If another person inhales those virus particles, the infection cycle can start again within their respiratory system.
6. Checking Understanding: The SARS-CoV-2 infection cycle
That’s a lot of detail. Let’s consolidate what you’ve learned with some interaction.
[h] SARS-CoV-2 Infection Cycle
[i] A Biohaiku
Smaller than dust in the air
Remember your mask!
[q] In the diagram below, what letter or number represents a ribosome?
[q] In the diagram below, the ACE2 protein is represented by which letter?
[q] In the diagram below, RNA replicase is represented by
[q] In the diagram below, which letter represents viral proteins in the endoplasmic reticulum before they’ve been assembled into new viruses?
[q] In the diagram below, what number shows the formation of new viruses?
[q] In the diagram below, what number shows the components of a new virus being brought together inside a vesicle? Note: this vesicle is more correctly referred to as the ERGIC (the ER-Golgi intermediate compartment).
[q] In the diagram below, which number shows spike protein binding, followed by receptor-mediated endocytosis? .
[q] In the diagram below, which number represents exocytosis?
[q] In the diagram below, what letter represents the endoplasmic reticulum?
[q] In the diagram below, letter D represents a [hangman], letter E represents [hangman], and letter F represents an enzyme called [hangman].
[q] In the diagram below, letter G is labeled as “viral genomic RNA.” By contrast, “H” represents RNAs that code for viral [hangman].
7. How does SARS-CoV-2 cause disease?
The severity of disease caused by SARS-CoV-2 varies widely. About 20% of those who become infected show few or no symptoms at all (PLOS Medicine). While that sounds great, people who are asymptomatic (without symptoms) are still producing and exhaling the virus, enabling it to spread to others. In fact, transmission of the disease from asymptomatic people might be a major driver behind the spread of the pandemic. (healthline.com). That’s one of the most important reasons for wearing masks. Masks help people from spreading the disease to others. When you’re around others, wear a mask!
In most other cases (Centers for Disease Control) the most common symptoms of COVID-19 are similar to those associated with other respiratory infections: fever, coughing, muscle aches, sore throat, and congestion. One symptom unique to COVID-19 — experienced by about 80% of people who get infected — is loss of taste and/or smell. If you’re interested in learning more about that, read this article in Scientific American. The link will open in a new browser tab.
In a small proportion of patients, the disease can become severe. While this can happen to anyone, serious COVID-19 disease is most likely found in people who
- are older;
- have underlying health problems like high blood pressure, diabetes, chronic lung disease, or heart disease;
- are immunosuppressed (which means that their immune function is reduced).
To learn more about risk factors, please read this article. The link will open in a new browser tab.
In those with more serious disease, the effects of SARS-CoV-2 are mostly — but not entirely — seen in the lungs. In these cases, the virus might be
- Directly damaging cells in the lungs.
- Causing an immune response that leads to too much inflammation. Inflammation involves the release of fluid and pus into infected tissues. While that can normally help beat back an infection, too much inflammation can cause fluid to over-accumulate in the lungs, a condition that’s known as pneumonia. Pneumonia impairs a patient’s ability to absorb oxygen into their blood, and low blood oxygen levels are a sign of serious COVID-19.
- Causing blood clots in the lung, which can further damage lung tissue.
Because SARS-Cov-2 affects the tissue lining the circulatory system, the effects of the virus can be seen throughout the body. These effects include:
- kidney failure and kidney disease.
- damage to the heart and cardiovascular system.
To learn more about COVID-19, please use the links below. Both links open new tabs.
- How does the coronavirus cause serious COVID-19 disease?
- This article on Wikipedia. (the link takes you to the disease section).
8. How do mRNA vaccines work?
A vaccine is a substance introduced into the body that stimulates the immune system to create memory cells. Memory cells remember the molecular structure of infectious agents. When your body gets infected again by the same infectious agent, memory cells enable the body to quickly fight it off: so quickly that you don’t even know you’ve been infected. That’s what it means to have immunity so something.
The counter attack led by memory cells is what’s known as the specific immune response (which you can learn about by following the previous link). All you need to know for now is that the specific immune response enables your body to produce:
- Antibodies: proteins that bind with an infectious agent (like a virus) and neutralize it before it can do any damage.
- Cytotoxic-T-Cells. These cells, also known as Killer-T-Cells, can find cells that have been infected by viruses, and wipe them out. This prevents the viral infection cycle you learned above above from spreading to more cells.
Vaccines have been in use for over 200 years. They prevent diseases that once caused millions of deaths (particularly among children) each year.
A variety of vaccines have been developed to help us create immunity to SARS-CoV-2. You can learn more about vaccines at this page on the NY TImes. For two reasons, I’m going to focus on one type of vaccine: mRNA vaccines. The first reason is because the way they work is particularly relevant to what you’re learning in AP Biology. The second reason is that two leading vaccine candidates — the ones produced by the biotechnology companies Pfizer and Moderna — are mRNA vaccines. When you get vaccinated, these are most likely the vaccines that you’ll receive.
There are a few big ideas behind these mRNA vaccines:
- Unlike many other vaccines, mRNA vaccines don’t use weakened or killed virus to elicit an immune response. Instead, they use a short segment of the virus’s mRNA.
- This mRNA goes into some of your cells, which start to produce the SARS-CoV-2 spike protein.
- Production of that protein enables your immune system to learn to how to recognize and fight off the virus.
Here’s some more detail about how mRNA vaccines work.
In the diagram to your left, “A” represents the spike protein of SARS-CoV-2. That protein was coded for by one of the protein-coding genes in the SARS-CoV-2 genome. “B” shows the RNA for that spike-protein-coding gene.
To make an mRNA vaccine, that mRNA is isolated, and modified in such a way that it’s ready for translation by a ribosome. This modification happens naturally to your mRNA, but needs to be engineered into the structure of an mRNA vaccine so that the mRNA can be translated by your cells.
You can see this ready-to-translate mRNA shown at B’ in the large callout in the center of the image. At “C,” to the left of the S-protein mRNA sequence is a 5′ GTP cap. GTP is similar to ATP, but it has the nitrogenous base guanine instead of adenine. You’ve met GTP earlier in the course when you learned about the Krebs cycle and G-protein coupled receptors. To the right, at the 3′ end of the mRNA is a poly-A tail (shown at “D”). A poly-A tail consists of a repeated string of adenine nucleotides that don’t get translated into protein. What’s their function? The 5′ GTP cap and the poly-A tail both serve to protect the mRNA from degradation by enzymes in the cytoplasm.
Surrounding the mRNA is a lipid envelope, at E. This lipid envelope is what enables the viral mRNA to survive its trip through the bloodstream and to enter into a human cell.
“F” shows a vaccine vial. Millions of these vials will need to be distributed around the U.S. (or any country where the public is going to be vaccinated). “G” shows a hypodermic needle. A physician, nurse, or other trained technician will inject you with the vaccine. The vaccine will float around in your bloodstream until it encounters one of your cells.
This encounter is shown at H. Your cell membranes are composed of lipids, and since lipids dissolve in lipids, the lipid envelope of the vaccine will fuse with your cells, dumping the viral mRNA inside.
Once inside your cells, the viral mRNA will be treated like any other mRNA. A ribosome (at “I”) will come along and read the viral mRNA. The result will be production of the SARS-CoV-2 spike protein (at “J”). These proteins will then make their way to the surface of your cells.
At this point, I’m leaving out many steps. The key point, however, is that your immune system will identify this protein as what’s called an antigen: an antibody generator. Antibodies are proteins with very specific shapes, capable of binding to antigens and neutralizing whatever infectious agent has brought the antigen into your body. Antibodies are shown above at K, binding with the spike protein that’s on a the surface of a human cells.
The key point is that after you’ve been vaccinated, your immune system will be able to produce antibodies that will bind to the spike protein on the surface of SARS-CoV-2, as shown at left. The antibodies are shown at 2. They’re binding to viral spike proteins, shown at 1. And once they do, the virus can no longer infect human cells. It’s been neutralized. You have immunity.
9. Covid-19 disease and mRNA vaccines: Checking Understanding
[qwiz qrecord_id=”sciencemusicvideosMeister1961-COVID-19 Disease and mRNA Vaccines” random=”true”]
[h]Quiz: Covid-19 disease and mRNA vaccines
[q multiple_choice=”true”] True or false: if you don’t have any symptoms associated with COVID-19 (such as a runny nose or cough), you can’t spread the disease to others.
[q multiple_choice=”true”] True or false: if you can still taste or smell, you definitely aren’t infected with SARS-CoV-2
[q] A big problem experienced during COVID-19 is that an infected person’s immune system might react to the infection in a way that causes too much [hangman]. This causes fluid and pus to build up in the lungs, making it hard for someone to absorb enough [hangman] .
[q] The goal of a vaccine is to get your [hangman] system to produce [hangman] cells. These cells enable your body to quickly respond to and fight off an infection.
[q] Two vaccines that have been developed to fight COVID-19 both use the nucleic acid [hangman], enclosed within a [hangman] envelope.
[q] The big idea behind mRNA vaccines is that they get you cell to produce SARS-CoV-2’s [hangman] protein (shown at A and J). This enables your immune system to produce [hangman] to the virus (shown at K), enabling you to fight off subsequent infections.
[q] In the diagram below, mRNA coding for the spike protein is shown at
[q] The goal of an mRNA vaccine is to get human cells to produce a viral protein, leading the development of an immune response. In the diagram below, that human-produced viral protein is indicated by which letter?
[q] In the diagram below, the vaccine is shown fusing with a human cell at
[q] In the diagram below, the lipid envelope that protects the injected mRNA when it’s in the bloodstream and which lets it get into a human cell is indicated by which letter?
[q] The goal of an mRNA vaccine is to get the immune system to produce antibodies to the virus In the diagram below, these antibodies are shown at
[q] In the diagram below, a human ribosome is reading viral mRNA, producing a viral protein. That ribosome is shown at
[q] In the diagram below, a long string of repeated adenine nucleotides that protects the mRNA from enzymatic breakdown is shown at
[q]The diagram below shows a SARS-CoV-2 particle that’s been [hangman]. That’s because the [hangman] covering the spike proteins will keep the virus from [hangman] any more cells.
10. Staying Safe
At the time I’m writing this (early January, 2021) the rate of COVID-19 spread in the U.S. has risen to horrific levels — over 200,000 new cases/day. While the approval and distribution of vaccines provides hope that this pandemic will eventually come to an end, it’ll be many months before enough of us are vaccinated to stop the virus’s spread. I don’t have anything new to say about how to avoid infecting others or becoming infected yourself, so I’ll repeat what’s widely known.
- Wear a mask when you’re around others. Your mask protects you a little bit. More importantly, by keeping any virus you might be producing under your mask, it keeps you from infecting others.
- Maintain distance. The closer you are to someone else who’s infected, the higher the concentration of virus that you’ll breath in. The reverse would be true if you were infected. Keep your distance to avoid spreading the virus.
- If you are working indoors in the presence of others, wear a mask, and keep the room that you’re in well ventilated.
That’s it. Stay safe. Avoid infecting others. Avoid becoming infected yourself. If everyone in the U.S. woke up every morning saying to themselves “I’m going to do everything I can to avoid infecting others and to keep from being infected,” we could save many lives.
11. Exploring Further
It’s painful for me to stop this tutorial at this point. There’s so much biology — especially evolutionary biology — that I haven’t covered. But that doesn’t mean that you can’t go on and learn it. I found these links to be particularly useful as I was researching this topic, and I encourage you to go ahead and explore.
- Coronavirus explained (links to multiple webpages, including “Getting to Know the New Coronavirus,” which has an excellent 3-D depiction of the virus)
- Sars-CoV-2 by the Numbers
- Wikipedia: Severe acute respiratory syndrome coronavirus 2
- HHMI Biointeractive, Biology of SARS-CoV-2
- Coronavirus Vaccine Tracker (NY times)
- How Pfizer’s [mRNA]Vaccine Works (NY Times)
- From Bats to Human Lungs, The Evolution of a Coronavirus (the New Yorker)
This tutorial ends this module about Viruses. Please choose another tutorial from the menu above.