Specifics of the coronavirus protein and receptor

Membrane Protein Structures of S Protein and ACE2 Receptor

S protein is a homotrimer classified as a type I transmembrane protein and a class I viral fusion protein (Huang et al. 2020; Pillay 2020). S consists of two main subunits, S1 and S2. The globular head contains the S1 N-terminal RBD which is used in the recognition and binding to the host ACE2 receptor while the stem contains the S2 C-terminal membrane fusion domain to mediate cell membrane fusion of SARS-CoV-2 with the host cell (Huang et al. 2020). S is oriented with a long extracellular N-terminus and a short intracellular C-terminus anchored by a single transmembrane (TM) domain (see Figure 4A) (Huang et al. 2020). S exists in a metastable conformation but undergoes significant conformational changes upon binding and interacting with ACE2 (Huang et al. 2020). The binding of S1 exposes a cleavage site within the S2 domain that is acted on by proteases such as TMPRSS2 (Pillay 2020).

There are several post-translational modifications in the S protein (Pillay 2020). The outer surface of S is heavily glycosylated with heterogeneous N-linked glycans, which likely play a role in mediating host attachment, influencing priming by host proteases and antibody recognition (Pillay 2020). There are also several cysteine residues found in the cytosolic tail of the protein, which undergo palmitoylation (Pillay 2020). Their likely role is to mediate the protein-protein interactions between S and the ACE2 receptor when binding.

The cleavage of the S1/S2 domains is important for the function of S. The cleavage site located between the S1 and S2 domains contains several basic arginine amino acid residues (Arg-Arg-Ala-Arg at residues 682-685) (Pillay 2020). Positively charged amino acids are likely useful in positioning the protease for cleavage via electrostatic interactions (Law et al. 2006).

ACE2 is a dipeptidyl carboxypeptidase classified as a type I transmembrane protein, with a single TM domain (see Figure 4B) and a zinc- and chlorine-binding domain (Pillay 2020). It is oriented with an extracellular N-terminus and intracellular C-terminus, like S (Pillay 2020). ACE2 is expressed most in nasal pathways as well as organs such as the lungs, intestine, and heart (Jin et al. 2020).

As seen with the S protein, there are also several post-translational modifications in ACE2. A study done by Sun et al. (2020) identified multiple hydroxyproline and methylated sites in the human ACE2 receptor. These methylated sites result in a loss of charge and thus increases their hydrophobicity (Sun et al. 2020). Methylated sites may also have some role in elevating gene expression (Misra et al. 2020). The hydroxyl groups in the hydroxyproline sites are likely meant to increase the hydrophilicity of proline in its extracellular region on ACE2. Other common post-translational modifications such as phosphorylation, acetylation, or fatty acid acylation were not identified (Sun et al. 2020).

Biochemistry of a SARS-CoV-2 Variant: B.1.1.7

The SARS-CoV-2 virus variant strain B.1.1.7 belongs to a lineage that was first identified and isolated in December 2020 in United Kingdom (Galloway et al. 2021). It soon became a variant of concern (VOC) due to its rapid spread in the UK and its arrival to the US.

B.1 is one of the earlier parent variants of SARS-CoV-2, from which B.1.1.7 arises. The B.1 strain developed a fixed mutation D614G (amino acid change from Asp to Gly at the 614th position in the RBD of S protein), which binds to the human ACE2 receptor more efficiently (UniProt 2021b). When cultured in human epithelial cells, the mutation aids in the production of infectious particles while causing no shift in the viruses’ inherent neutralization properties (UniProt 2021b).

On top of the D614G mutation, there are two other main amino acid mutations in the S protein, which are E484K (Glu to Lys at position 484) and N501Y (Asn to Tyr at position 501). The E484K mutation reduces neutralization by affecting the binding of serum polyclonal neutralising antibodies, while the N501Y mutation has been shown to enhance affinity to the human ACE2 receptor (Galloway et al. 2021; Jangra et al. 2021). Results from a paper published by Santos and Passos (2021) indicated through experimentation that the mutant N501Y established stronger interactions with residues Y41 and K535 on the ACE2 receptor. A combination of these mutations allows for enhanced and more efficient viral entry into the host cell, the overall resistance to antibodies, the latter of which raised concern over the efficacy of existing COVID-19 vaccines. Several other amino acid mutations such as A570D, P681H, T716I, S982A, D1118H target the S protein; however, they have not been extensively studied (Galloway et al. 2021).

More about COVID-19

COVID-19 is a disease caused by the novel coronavirus SARS-CoV-2. SARS-CoV-2 reportedly originated from bats in an animal market in Wuhan, China, where the outbreak of the virus first occurred. The disease has since been documented in individuals of all age groups, with infection severity ranging from asymptomatic to critical condition to even death. Comorbid cases are more fatal and there is also an age-related susceptibility to the virus with elders developing more critical COVID-19 conditions. Further, certain populations of individuals are more susceptible to the disease including ethnic populations such as those from the Black and Asian community.

SARS-CoV-2 is an enveloped, positive-sense single-stranded RNA virus that is a member of the β-coronavirus family. The SARS-CoV-2 genome encodes for various major viral proteins, some of which are structurally important such as the E (envelope), M (membrane), N (nucleocapsid) and S (spike) proteins. Of these, the S protein is critical for cellular entry by facilitating the attachment and fusion of the viral membrane with the host cell membrane. SARS-CoV-2 gets its Coronavirus (corona: crown) name from the glycosylated S proteins protruding from the viral surface. S protein contains a receptor-binding domain (RBD), a fusion and a transmembrane domain. In humans, the RBD of S binds to the angiotensin converting enzyme 2 (ACE2) receptor, facilitating viral entry in cells. ACE2 receptors are present in a wide variety of human cells including those lining nasal pathways, the lungs and ileum, making these some of the primary target areas. Given that the main transmission route of the virus is through respiratory droplets and/or physical contact with an infected individual, the nasal and lung pathways allow for easy viral entrance and attachment to host cells.

When the S protein binds to the ACE2 receptor, a TM serine protease (TMPRSS2) cleaves S between its two subunits (S1 and S2), thus activating the protein to enter the host cell, which it does upon altering the conformation of its spike. After proteolytic cleavage of S and release of one of its subunits (S2), fusion of the virion and endocytosis can occur. Upon virus entry into the cell, viral RNA is released, and host cell machinery is utilized for replication and transcription of the viral RNA genome. SARS-CoV-2 needs both the S protein and the ACE2 receptor to facilitate cellular entry of the virus for the purposes of its transmission, propagation and spreading in cells and tissues within the body. The interactions of these two proteins leads to a host of physiological changes in the body, including pneumonia-like symptoms of fever, headache, coughing and body pain.

SARS-CoV-2, upon gaining access to the host cell machinery, is initially detected by pathogen recognition receptors (PRRs) which then elicits enhanced interferon production. Like previous SARS-CoV and MERS-CoV infections, the humoral response against SARS-CoV-2 involves characteristic IgG and IgM antibody production. An observational study detected anti-S-RBD IgG in all 16 of the study’s SARS-CoV-2 patients, with additional reporting of anti-N IgG, anti-S-RBD IgM and anti-N IgM antibodies but in slightly decreased presence.

Note: if you’d like to see a complete list of references, you can always email me and I’d be happy to share it!

Finishing my first-year of university

It’s been a couple of weeks since I’ve finished my last exam from my set of Winter term classes.

Now that it’s summer, I’ve had some time to reflect on how this past academic year has gone for me. I’ve also been able to reflect on things that did or didn’t work for me as a new university student as well as make sense of my high school to university transition.

In this post, I intend on sharing a bit of what I’ve been thinking about these past few weeks.

Starting university back in September involved trying to figure out a lot of different things at once. I went from being a Grade 12 graduate enjoying my spare time with family during lockdown to being a full-time first year student at university with a demanding work load. In the early days of the Fall term I had, in some ways, convinced myself that I had forgotten what it meant to be a student, let alone a “good” one. I had been out of “regular” school for the better part of six months, so it definitely took some time to switch into the proper gears…the type of gears that would allow me to excel in my first year of studies.

I’m not going to sugarcoat it…navigating online school was quite difficult. It was an interesting experience going from summer and no school to then having to become familiar with all the online platforms that were being used as part of my classes. I remember it taking me a couple of days to just get a hold of myself and to organize my virtual space and all that was required of me for each one of my classes. I quickly learned that high school and university were quite different from each other. I was just as stressed, but now there were higher expectations and the onus was fully on me to read, understand the material and reach out for help when I needed it.

Each class was also being taught in a unique way, something that I hadn’t really experienced before. At times, it was difficult for me to acknowledge and attribute where my stress or feelings of anxiousness were coming from. Was it the high school to university transition, or because everything was online? This was the source for a substantial amount of my initial frustration. However, once I got busy with lectures, weekly assignments and midterms the frustration and anxiousness subsided and I was just enjoying my time learning and being a student, a feeling I’m very comfortable and familiar with.

As the term progressed I realized that I was able to get a better handle of things. I was able to better organize my time and follow a schedule so I didn’t fall behind in any of my classes. It did take some time but by the time the Winter term came around, I felt much more at peace with the transition and I could focus on the content earlier on in the term.

If I took anything away from my first year of university, it’s that I learned to roll with the punches and adapt to a whole new learning environment just like the rest of my peers. That’s pretty cool, right? In the process, I also learned more about what it meant to be resilient: bouncing back from a bad grade, a bad day or a bad week was very important.

Overall, this past academic year has been new, challenging and exhausting to all students to say the least, but upon reflection, I think there was much more to take away than it might seem.

The importance of health literacy

Let’s face it, COVID-19 has snatched something or another from all of us. But, it’s also done something pretty important: it’s brought the focus and attention to our public health systems. It has also exposed the relationship between said system and our society especially, when it comes to doing the right thing with access to health-related information. This is where health literacy comes in.

Health literacy isn’t just about being up to date with case numbers and what’s going on in the news. It’s not even about knowing a bunch of scientific terminology, which you might not even fully understand. It’s not about dictating what other people should be doing to protect themselves or things that they shouldn’t be doing. Health literacy is much more than all of this.

Health literacy means taking the time to educate one’s self about making informed decisions to protect ones health. With a large outbreak, such as the one we are currently facing or as was the case with other viruses in recent history, being able to read up about precautionary measures is essential. We need to protect ourselves before we can worry about enforcing rules to protect others. This is analogous to a plane procedure they go through with passengers about putting your mask on yourself before helping anyone next to you. We are part of the problem if we can’t even keep ourselves safe. It is important to understand this.

You should also keep in mind that anecdotal evidence is not really a good indication of what will or will not work for you. For example, individuals that oppose vaccines have claims that are largely anecdotal. If you ask a group of these people about some of the sources they have consulted, you would be intrigued to discover that these sources are not all that credible and are heavily reliant on anecdotes. Or while they may credible, they might not be upholding the right practice of academia. This is a whole other issue that I don’t have the time to delve into.

Largely, misinformation contributes to a weakened public health response. Misinformation contributes to panic and flashy headlines in online sources. Misinformation is dangerous and we as a society need to do more to help stop its spread as well.

Now, I’m not saying you need a Bachelors in science to understand science related information that is available in our digital age. All I’m trying to say is that with health literacy, you just need common sense and the willingness to consult a wide variety of sources before coming to any brute decision. And with the whole world at our fingertips, I don’t think this should be much of a problem. Start to actively take steps to fight misinformation and develop a strong sense of health literacy with you and your loved ones. Make sure you know how to keep yourself safe during this pandemic and attempt to do it for the right reasons.

To that end, please wear a mask, wash your hands and stay socially distant. We can all do our part to keep ourselves and everyone around us safe.

Finding Self-Worth: University Addition

Applying to university can be a nightmare and a dream come true at the same time. With senior year marking the start of the end of your high school career, much thought goes into the next step of our lives, which may play into our future successes. For many, this includes post-secondary plans such as attending a college or university.

For me at least, applying to university was an experience I was very much looking forward to. And like just about anybody else in my shoes years before me, I had a ton of questions: how do I even apply to this school? How do I keep track of everything? Am I good enough to get into this school? Are my grades and test scores enough? How do I approach writing this essay? And as you can probably imagine, the list goes on and on and on.

This is just a quick snapshot of all the questions and thoughts that were running through my mind at the time. As you can see there were so many questions with answers that I couldn’t seem to find or figure out on my own. If you are a senior in high school this year, I’m sure some of these questions (and more!) have popped into your head at some point or another. It might seem daunting and a lot to handle all at once but you should know that this is completely natural and even part of the whole process.

Now, in this post, I don’t intend on going over tips and tricks on things like applying to schools in Canada and getting into T20 schools in the US like I, fortunately, managed to do: that’s not very helpful in the long-run. Instead, what you need to know and hear about is more related to not equating self-worth to your admission into a particular school. Regardless of the schools you get into, the schools you get rejected from or the schools you get waitlisted from, you need to understand that you are not lacking in any way. If you have done everything in your capacity, know that there isn’t more that can or should be done.

University Admission Officers are people too you know. They can see through the “real” applications as well as the “fake” ones. They can get a good idea of things you are actually passionate about and things that you maybe aren’t so passionate about. This is all part of the real you and manufacturing parts of yourself might be really obvious to some of these admission officers. Now, I understand that you may have worked to the best of your abilities in high school and are nervous about the outcomes but you shouldn’t worry. Where you go to university doesn’t dictate who you are and it certainly doesn’t limit who you are. If it did, then great people would only be coming from schools that you deem “good” enough. Take a moment to think about whether this is true or not. I bet you this is not the case.

Now I’ll admit, too many times during the application process, I questioned my abilities, how good I was and how good I could be, what I liked and what I really didn’t like. At the time, this didn’t seem very detrimental but in fact, it was. You see, thinking you aren’t good enough for someone or something becomes this barrier that I, myself, was just trying to overcome. And since you are almost always your own harsh critic, it can seem impossible to break out of that circular argument and appreciate all you have done and all that is left to continue working towards.

In a nutshell, applying to university is a rollercoaster ride. You may be happy with where you end up, or you may not be. I certainly hope its the former. However, wherever you do end up and wherever it takes you in life, just know that doubting yourself was never part of the equation and it was never meant to be.

The Hierarchy of Power

Maybe it’s because I’m a woman. Maybe it’s because I’m a minority. Maybe it’s because I’m a teenager and I’m still in school. Maybe it’s because I’m “not old enough” or that I “don’t have enough experience”.

Around us, wherever we go, the presence of a societal hierarchy of power can always be felt. It is something that is always evident and if it’s not evident then social norms make it apparent. Through my eyes, this is both problematic but necessary for the proper function of society.

Power as defined by Merriam-Webster Dictionary is the “ability to act or produce an effect.” As such, having power is positively connotated because it can be used to bring about positive change in society. In majority of cases, I support this notion: that power helps bring well-needed change. However, I’m not dismissing the idea that just because you have power you are aiming to benefit society at large.

In majority of cases, authoritative power has done great things for society. It helps communities, encourages good behaviour and sustainability of the environment, and can save lives. An example of this might be how Asian countries such as Taiwan and Vietnam were quick to follow public health guidelines and shut down their borders to slow the spread of COVID-19. Such preventative measures were employed by the government and public health officials as a whole; however, the thought must’ve come from somewhere. In this case, power, cooperation and coordination worked in harmony to give death counts below seven, among populations of millions and millions of people in those countries.

On the flip side of this argument, media sources, the news, interviews, and just about any type of information outlet have highlighted the ways in which authoritative individuals–who have earned or been given powerful positions–are misusing their power to address a personal agenda. A prime example of this would be sexual assault offenders that were brought into the spotlight because of the #MeToo movement. Men such as Harvey Weinstein got away with years of abuse towards women, many of whom came forward with traumatic recollections.

It is these instances that make me question the thought of giving individuals massive amounts of authoritative power. This designated power guides them up to a pedestal, sitting comfortably above everyone else. The problem with sitting on a pedestal is not that they sit higher than others who work for or with them, or that they haven’t earned what they’ve worked for–because working hard would have been part of the equation–but that this power makes individuals immune to making mistakes in the public eye. Hush money, illegal contracts made decades ago and other things of the like contribute to this negative use and abuse of power.

Now, these examples are much larger than maybe you and I for example, but they accurately demonstrate both sides of the same coin. For those of us that just go about our day-to-day lives, societal hierarchies are evident in the form of interactions. As a teenager and student, I, for instance, might face scrutiny for being disrespectful to an adult when trying to voice my own opinion. Adults are older than the average teenage student and hence hold more power than we might. In many cases, being older correlates to more wisdom, experiential knowledge, and power but having less “societal power” doesn’t make you any less of a human being. While I’m a firm believer that elders should be respected for all they’ve done and continue to do for us, power differences shouldn’t be something that hold you back. After all, opinions can be voiced in a manner that is kind and respectful!

With that being said, it seems that power, in general, is necessary for a society to grow and become better. It may be used for the benefit of others, or it may not, but, having and exercising power is one of the main reasons that law and order is maintained. And remember that this isn’t just about government and authority figures having power, but also includes citizens. We are a large part of society and the decisions we make and work in accordance with allow us to exercise our own power.

Graduating from high school during a pandemic

I have only ever been to two graduations in my entire life. Both of them were eighth-grade graduations: mine in 2016 and my sister’s in 2018. June 2020 was a signal of my upcoming graduation from high school; however, much like the rest of my fellow Class of 2020 students from my school and around the world, I too missed out on my Grade 12 graduation. Instead, many of us were addressed and congratulated by former President Barack Obama and other celebrities…through a screen.

Before the COVID-19 pandemic hit, I was excited to get the once in a lifetime opportunity to commemorate my time in high school by attending my graduation. I had worked hard for it and it would have given me a chance to celebrate all that I had accomplished over my four years there. Little did I know, I was completely wrong. There was no fancy graduation, just an anti-climatic finish to everything that was supposed to be just the opposite of anti-climatic.

Instead of celebrating my graduation “explicitly” with caps and gowns and a traditional ceremony at a rented-out hall, I found myself “celebrating” all the things I was fortunate enough to even be able to do, things that I may have taken for granted. Waking up and spending the majority of my time in the four walls of my home, I was forced to adapt to a latter half of a senior year that involved not being able to see my friends in person, and taking cumulative tests and exams online. My IB exams were reduced to nothings and my Diploma was riding on the fact that I just keep my grades up from what they were before we had “left school”.

Time seemed to move slower than I had previously thought. My days: longer. My motivation: close to zero. My hope for life to return to some form of normalcy: slowly diminishing. My graduation and prom: running farther and farther away from me as March, April and May passed by…slowly.

This may seem very miserable to you but I will assure you that it was not as bad as I make it seem. These past several months, while a bit boring and lonely, have allowed me to reflect and slow down in a way that I have never been able to do before. The exciting part about all of this is that I have been doing this all from the comfort of my own home.

Considering that the world pretty much slowed to a stop, I was finally able to catch up with myself and check in to see how I was really doing. Sure, I was upset that I was missing out on so much typical of a senior year in high school, but knowing that I wasn’t the only one feeling this way made the process that much more bearable.

High school–as cliché as it sounds–is supposed to help you find out who you really are and what you’re all about. Even without a graduation, I think I was able to learn a lot about myself. Now, I will admit that I was yearning for some sort of closure as I begin a new chapter of my life soon, but that doesn’t mean that I had to be ungrateful in this process.

While my brain will forever associate my high school years with this pandemic, I think my reflections enabled me to see past what the virus took from me. Such a mindset is very selfish of me. What this whole process did was it helped me become aware of the happenings around the world, especially of those that didn’t directly involve me, or that were quickly developing and that needed my attention in order to be solved. While it can be all too easy to hold a grudge and remain frustrated with an undesirable outcome in life, remaining positive and trying to take the high road will serve us better in the long run.

Then in this case, I guess graduating from high school during a pandemic wasn’t as terrible as I thought it would be…

Greta Thunberg: The face behind the climate youth strike

As a global society, it’s safe to say that climate change has been the elephant in the room at large political summits with potential actions but a whole lot of fake promises. And with hundreds of reports released on our planet’s state, it seems as though all this talk about our planet has kept reaching dead ends. Enter Greta Thunberg.

A little over a year ago, Greta Thunberg, was just your average teenager, she went to school, had friends and did her homework. However, little did people know that Greta had a strong passion for the environment. She was a witness of the climate trends favouring the irreversible changes to our climate that would become a reality in the near future. She knew that the mistreatment of the only planet we have to cherish and live on, was wrong. In protest, she skipped school and sat outside of the Swedish parliament every Friday for almost a whole year. It could not be more obvious that Greta knew what it meant to take a stance and bring attention to our planet’s condition by casting a different kind of light on the situation. She clearly wanted to make a difference, and she was doing so by defending her beliefs.

Many of you must be familiar with a largely shared Instagram post of Greta speaking at the United Nations conference a couple of weeks ago. The videos have garnered millions of views alone through Instagram with tweets, shares and reposts on other social media platforms further increasing the number of interactions with the subject. Regardless of the views it has received, it’s important to recognize and the courage that it takes to talk in front of such a large audience of reputable individuals while also criticizing them for chasing profits rather than chasing the companies, individuals or unhealthy practices that are largely contributing to the very-familiar climate crisis. Not only has Greta demonstrated the courage she has to speak up but we also find out about her dedication and willingness to maturely discuss important issues regarding our planet. In return, Greta has sparked many topical discussions surrounding practical climate change solutions by marking her presence and being accountable.

In a time when we desperately need action from politicians to put actions into words, Greta could not state the scenario any better: “You have stolen my dreams and my childhood with your empty words.” For many protesters with the same intentions as Greta, politicians have stolen their dreams as well. The dreams of future generations may also be stolen if Earth becomes a planet that is no longer suitable for life. This would be very unfortunate; however, not far from the truth. All I’d like to say is that please continue to use your voice for the better so politicians will need to come to us for solutions when they don’t have the answers.

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Go Green

Do you ever think about what our world would be like if we went completely green? Now, I’m not talking about the green as in planting so many trees we aim to regrow forests, green. While that is very good, I might be criticized for not being realistic with you. In any way, I’m talking about the new generation’s craze with green energy.

To clarify, green energy is a renewable source of energy that incorporates solar, wind, geothermal and nuclear energy sources. They are beneficial to our planet because they are replenished in a natural manner without much harm to others around us. Non-renewable energy sources don’t directly impact humans but they will eventually when pollution levels become toxic to live in. I hope this never happens but the news tells otherwise.

On Wednesday, the Green Party of Canada released its plan to help workers in the fossil fuel industry transition to the renewable energy industry. This comes with some sighs fo relief given the social media posts claiming we only have 18 months till our planet will suffer from actions that are irreversible. I’m not sure how we should be reacting to this considering we have been told to clean up our acts for a couple of years now.

With people like Greta Thunberg headlining environmental news every other day, I am hopeful that there is something we will be able to do to lessen the impact of climate change on Earth. However, it seems difficult to do so among the noise that distracts our focus away from environmental issues. If 18 months is all we have left before we settle into an irreversible period, I vote that we should try to at least focus on issues that aim to deal with the actual problem at hand: climate change.

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