The Science Behind the Coronavirus PART TWO

An Interview with Biology and Chemistry Teacher Mr. MacNichol

The Science Behind the Coronavirus PART TWO

Hannah Gao, Staff Writer

To better understand the science behind the COVID-19 virus, I interviewed (through email) Mr. MacNichol, a Harriton biology and chemistry teacher who is knowledgeable about the science of this disease. Read on for the rest of our interview.

Does genetics have a role in how different people’s bodies react or deal with COVID-19?

Absolutely! There are many factors that influence how susceptible an individual is to a viral infection and genetics can certainly be one. If you look at the way SARS-CoV-2 enters your cell (through the ACE-2 receptors), it is possible that small variations in the ACE-2 gene could make it easier or harder for the virus to enter into cells and, from this one study alone, it appears that at least 17 unique versions of the ACE-2 protein exist in the human population. It very likely could be that some of these versions are more susceptible to infection than others, a concept that has already been proven true in the case of another cell receptor, called CCR5, and HIV susceptibility.

Individuals who are homozygous [or have identical alleles of a gene, one from each parent] for a version of this receptor called CCR5-delta-32 are essentially immune to HIV. Interestingly, this version of the CCR5 receptor is found mostly in people of European descent, and it is thought to be the result of a selective pressure that dates back to the black death nearly 700 years ago. Contrary to what most history books tell us about fleas on rats, the black death is generally considered to have been caused by an ebola-like virus. Individuals with this mutated version of the CCR5 likely were immune to that as well.

In addition to differences in our ACE-2 receptors, scientists are also investigating the potential effect of differing HLA (human leukocyte antigen) complexes, which are genes responsible for regulating our immune response. Every human has 6 major [gene] regions in their DNA that code for their HLA complexes. With hundreds of different versions of these genes in our population, but only 6 in any one individual, the immune systems of our population have tremendous diversity.

Another interesting study that people are reviewing currently was a finding from Wuhan, China that looked into the blood types of people infected with the virus and compared it to the frequency of those blood types in the population. Early results suggest that type-A individuals were infected at a higher frequency than expected based on their relative frequency in the population, while type-O people less so. It’s important to note that these early findings are pre-print findings, meaning scientists have not had the opportunity to peer-review their results and methods. While this is an interesting assertion, it would be inappropriate to put too much weight into their findings currently.

One final point is that the gene for the ACE-2 protein is located on the X-chromosome, meaning that biological (XY) males would only have one copy of this gene while biological females (XX) could have two copies of this gene. Females having two copies may lead to a greater expression of the ACE-2 receptor on their cells, which at first may seem like a negative. However, biology can be more nuanced than you may expect. The ACE-2 receptor is also part of the immune response, and when the virus binds to the receptor it also effectively removes it from the membrane. Having more receptors prior to infection would mean there would be more leftover after infection to initiate a beneficial immune response. Currently three males die for every two females from COVID-19. Could this partially explain the disparity in deaths by sex? Genetics may play a small role in this biological sex difference, however my guess would be that it is more likely due to lifestyle and other environmental factors.

How do vaccines generally work to protect people against viruses?

A vaccine incites active immunity by tricking the immune system to think it has an infection, usually by exposing your body to the viral antigen — in this case the spike protein. This typically occurs in one of three primary ways:

Exposing the patient to the actual virus either in a weakened but active state or a deactivated version. The closer the vaccine is to the real thing, typically the stronger the immune system’s response will be. However, if the vaccine is too close to the real thing, it can be too dangerous to give to immunocompromised individuals or people currently undergoing treatment for cancer.

Exposing the patient only to the viral antigen subunit. The University of Pittsburgh is currently developing a patch that has tiny microneedles with SARS-CoV-2 spike proteins on the end. This patch is brushed across someone’s skin, introducing the spike protein to their system and inciting an immune response.

Injecting a synthetic mRNA sequence that codes only for the SARS-CoV-2 spike protein into the patient’s cells. The recipients’ cells will translate the mRNA into protein and their immune systems will respond and develop immunity against subsequent encounters with the protein.

I’ve seen stories about treating people with plasma from those who have recovered. Is this an effective treatment? What are some potential treatments for COVID-19?

This treatment, called convalescent-plasma therapy, is actually an effective treatment for some viruses that dates back to the influenza pandemic of 1918 and in some ways predates humanity. As it turns out, all young nursing mammals acquire plasma antibodies through breast milk, a vital transference of immunity from mother to baby before the child is able to actively produce their own antibodies.

The concept is simple — recently recovered patients have a lot of antibodies flowing through their blood. If they were to donate their blood plasma to a sick patient, the antibodies in the plasma could infer temporary immunity. While this does not give the same degree of immunity as a vaccine because the patient isn’t yet producing their own antibodies, this can buy valuable time early in the infection.

In addition to convalescent-plasma therapy, several antiviral therapies also show potential for helping with this crisis, although none have been confirmed to be effective yet.

One treatment, called Remdesivir, acts as a nucleotide analog which is a fancy way of saying that when the RNA polymerase goes to add new nucleotides to build the viral RNA genome it adds remdesivir instead. This jams up the RNA dependent RNA polymerase enzyme, preventing the copying of the viral RNA. Research in the Journal of Biological Chemistry suggests that Remdesivir may actually have a greater affinity for the polymerase than even natural nucleotides, meaning it could be very effective.

Another treatment, called Hydroxychloroquine, is a weak organic base that changes the pH of the cell and certain cellular organelles, making them less acidic. Many cellular processes occur at specific pHs, [so] by altering that pH, Hydroxychloroquine can disrupt these cellular processes. In other clinical trial applications and in studies with SAR-CoV-1, Hydroxychloroquine has shown the ability to limit the binding of the spike antigen to ACE-2 receptors and thereby inhibit the uptake of SARS-CoV-1, inhibit replication of SARS-CoV-1’s genome, and temper the violent immune response called a cytokine storm that can often be associated with severe acute respiratory disease.

Do antibiotics have an effect on viruses?

Bacteria are truly living, having all of the machinery to run their own metabolism, maintain homeostasis, and replicate themselves. Viruses are essentially dormant DNA or RNA programs that need a host cell to activate their metabolism and replicate. Since bacteria are living, antibiotics can be very useful for stopping a bacterial infection.

While there are many different types of antibiotics, all are chemicals that kill or immobilize the bacteria by preventing some critical process such as cell wall formation, protein synthesis, or replication. With these critical processes deactivated, the bacterial cell can no longer maintain homeostasis and quickly die. Our general macrophage white blood cells then go around and clean up the remaining debris.

Since a virus is non-living, its metabolism and reproductive machinery lies dormant until [it is] inside the host cell. If a virus encounters an antibiotic chemical outside the host cell there is no metabolism or cellular process to disrupt since the virus is not alive — therefore antibiotics do not work against viral infections. Some rare viral infections can exhaust your immune system so much that it makes you more likely to develop a secondary bacterial infection. In this scenario a medical doctor may also prescribe an antibiotic in addition to some antiviral treatment should you get a secondary bacterial infection after your initial viral infection.

How long can the SARS-CoV-2 virus remain infectious outside the body? What affects how long the virus can survive?

According to a study by the NIH, CDC, UCLA, and [Princeton] in The New England Journal of Medicine the scientists found that (SARS-CoV-2) was detectable in aerosols for up to three hours, on copper up to four hours, on cardboard up to 24 hours, and on plastic and stainless steel for up to two to three days.

However an important caveat for the procedure used in this study – specifically in the case of the aerosol detection – is that according to the WHO, the Goldberg drum apparatus used to artificially aerolize the virus in this trial is “a high-powered machine that does not reflect normal human cough conditions” and therefore may be much more effective at aerosolizing the virus than normal conditions. This is an important fact since there is often a minimal viral dose needed to cause an infection, and given that [the] amount of viable aerosolized virus is cut in half every hour, starting with a less concentrated sample in a more real-life clinical scenario may drastically change the amount of time the virus can be aerosolized.

Are face masks effective in preventing this virus?

This is a hot topic that has been debated for a while by scientists globally. First, let me emphasize that in this time of low personal protective equipment levels it’s important that everyone leave our best facemasks for our frontline health professionals who need them most. Additionally, some studies suggest that improper handling of masks can even cause you to be more likely to infect yourself. However, assuming there were an endless supply of N95 masks and you knew how to properly handle [the] mask, it would be advisable for people to use them should they absolutely need to go out to public spaces.

Research on the National Institutes of Health’s website [showed] a 2003 report from Hong Kong where doctors at 5 hospitals who used N95 respirators had a statistically significant reduction in infection rate during the first SARS outbreak, and another study of over 3,000 health professionals showed a significant reduction in viral respiratory infections and droplet‐transmitted infections when comparing healthcare workers that continuously wore N95 respirators vs. a control group that followed the local hospital’s standard mask practice. This is important, because it suggests that continuously wearing an N95 mask may even be significantly better than typical mask practice, not to mention what the results may look like if the control group wore no masks.

Additionally, while there is a lot of evidence suggesting that small viral particles can be suspended in the air as an aerosol, some early research from the University of Nebraska suggests that airborne samples generally do not contain a large enough viral dose to cause an infection in cell culture tests. This suggests that most transmission comes from larger droplets projected from an infected person while sneezing (40,000 droplets/minute), coughing (3,000 droplets/minute) or even talking (600 droplets/minute). If this is the case that most transmission occurs through the spread of larger viral droplets then yes, a face mask would help to prevent the spread of the virus.

As for non-N95 face coverings, such as surgical masks, the research findings are varied. However, it appears that surgical masks and other face coverings likely provide some degree of protection from viral droplets (1, 2, and 3) but the primary reason for wearing them is that they significantly reduce the risk of you infecting others. Anecdotal evidence from South Korea suggests that in addition to wide spread testing and aggressive contact tracing, their early adoption of facemask use may have been a contributing factor in flattening their curve when early infection data looked eerily similar to places like Italy and the United States.

What biological effect does hand soap and hand sanitizer have on the SARS-CoV-2 virus?

SARS-CoV-2 has an outer lipid and protein envelope that houses the inner RNA genome and facilitates entry into your cell. If this layer is broken apart, the virus cannot infect your cell. Soap does exactly that. Soap is an amphipathic molecule, meaning it has a hydrophobic end that attracts lipids and a hydrophilic end that attracts water. One side of the soap molecule will pull on the viral envelope while the other pulls on the surrounding water, and the tug of war pulls apart the viral envelope making it incapable [of infecting] your cells.

Hand sanitizers typically contain at least 70% alcohol by volume. Alcohols denature – or change the shape of – the viral proteins embedded in the viral envelope. If the viral proteins do not have the correct shape they can not bind with the ACE-2 receptors on our cells and therefore infection cannot occur. Remember the idea of an enzyme lock and key from biology? That same specificity applies to the spike protein and ACE-2 receptor binding. If you bend the key, it won’t fit in the lock and the door stays closed!

Will this virus die down in the summer months?

While I had originally hoped that to be true at the onset of this virus, the current spread of the virus in places like New Orleans suggests that will not be the case. The temperature in New Orleans regularly gets into the high 80s already and the virus does not seem to have any problem spreading in that condition.

Will the same COVID-19 virus come back in the future? Is there a seasonal or yearly pattern to it?

This past February, my four year old daughter was sick with the H1N1 influenza virus, strain-A. A lot of people don’t realize that this is essentially the same virus that caused the 1918 pandemic — it never left. This is also the virus that jumped into pigs temporarily and learned some new tricks, causing the swine flu pandemic. My point is that once viruses infect a large enough portion of the population, it’s very hard to ever get rid of them without an effective worldwide vaccination program. This is why there is almost no doubt that this will continue to spread around the world until an effective vaccine is developed. There are already over a million cases worldwide and the virus will continue to jump from population center to population center until either everyone has been exposed (not a good plan) or we can develop an effective vaccine to prevent infection. Assuming we get an effective vaccine, whether or not this becomes a periodic or seasonal event depends on how quickly the virus mutates, rendering that vaccine ineffective. Typically the flu mutates quickly enough that a new vaccine is needed every year, however this virus has a slightly slower mutation rate and so possibly a new vaccine will be needed every couple of years.