What Lies Underneath The Crown: Demystifying the COVID-19 Pandemic

Tremble in awe! The world has been subjugated by the unseen crown. He lies in every waking moment as a shadow of death, yet he thrives on the breath of life. After biding his time, he has now surfaced as the one who shall test the iron of nations and the fortitude of men. Oh shall his visit be an insightful lesson or shall he serve a grim reminder?

There is no way to put it bluntly. For the past several months, the world, much less the Philippines, has recoiled from the impact of a full-blown pandemic. COVID-19 (Corona Virus Disease 2019) has swept through the continents with relative ease and its progenitor, SARS-CoV-2, (Severe Acute Respiratory Syndrome-Coronavirus-2) has yet to be unraveled in its entirety. Throughout our fight against this disease, we’ve opened our eyes to the harsh realities of battling a virus on such a scale. Much has been learned in the many frontiers of science and we must highlight the key data we’ve found.

A Heritage Shrouded in Mystery

He comes from a family of tyrants, all of whom prey on those who have exotic tastes. As our greatest minds toil with his origin, he carefully pulls strings of power.

After all the meticulous attempts at deciphering the genome sequence of SARS-CoV-2, researchers have started to figure out the crown’s origin story. It stands as the seventh member within a family of coronaviruses known as beta-coronaviruses and it shares most of its genetic makeup, almost 96% of it, with RaTG13, a coronavirus found in a specific bat sample. Although the common notion after knowing these rudimentary facts is to immediately blame it on the bat or Wuhan’s exotic animal trade to be specific, what we need to understand is the other 4% makes all the difference.

In the journal, Nature Medicine, a study headed by Kristian Andersen on the proximal origins of SARS-CoV-2 points out the two notable features in the genome. The first highlights the virus’ spike (S) proteins, noticing how it has a liking to a particular receptor, called ACE2, found in humans. The researchers note that its high affinity for human cells is downplayed by the fact that it creates suboptimal bonds. From their deductions, the spike proteins must have developed from natural selection. The second fact sheds light on a possible gene insertion or mutation creating what they call a polybasic furin cleavage site. What’s ominous about this modification is that when MERS-like (Middle-East Respiratory Syndrome) coronaviruses found in bats are given the necessary changes to have the aforementioned site, they could potentially infect human cells. From these observations, a dichotomy of ideas has risen to explain how the virus developed.

One hypothesis suggests that the virus resulted from animal to human transmissions and the subsequent natural selection within hosts. The consensus surrounding the inter-species gap is still unclear, with some speculating that an intermediate host, most likely a pangolin, must have aided the transfer. On the other hand, a more controversial idea proposes that the virus developed inside a laboratory. Though the researchers find the former explanation more probable than the latter, they state that new findings could bolster either side of the argument. It’s also worth noting that the first hypothesis has already been the widely accepted origin story but certain instances of figures in politics pushing the second have been quite the narrative.

A good example of this was seen when U.S. President Donald J. Trump accused the Wuhan Institute of Virology (WIV) as the source of the virus. These allegations may have led to the decision of the U.S. National Institute of Health (NIH) to cancel funding on the EcoHealth Alliance in New York City, which housed certain bat-related virus research from the WIV. Shi Zhengli, known famously under the moniker “bat woman” for her extensive research on bat and mammal coronaviruses, spearheaded the defense of the institute.

In an interview with Science magazine, she tries her hardest to dismantle such allegations and to provide genuine information to the public. She says that it is simply impossible that the virus was leaked from the lab since none of the staff and the students were infected. She also criticized U.S. President Trump for his decision, stating that it jeopardizes their line of work and that he owes them an apology. Her answers though were not free from skepticism, with many saying that her responses were carefully manipulated.

Amid the complexity of it all, finding the true origin story of this virus may provide vital insights on both easing the plight of this pandemic and preventing such catastrophes to happen again.

His Prophecy Has Been Fulfilled

Many have warned of his coming and now that he has appeared, we revel at our inability.

Along with dismantling the opposition, Shi Zhengli has also included the fact that these kinds of viruses have been ravaging human lives and economies for more than 20 years. We can all view this tragedy from a multitude of lenses and angles, but there’s a utility in perceiving it as a recurring pattern or motif. In some sense, this has been a complete deja vu of the SARS outbreak back in 2002 and the 2012 MERS outbreak.

The idea of these viruses as an emerging and reemerging force has already been discussed, as early as 2007, by an article in the journal, Clinical Microbiology Reviews. There’s quite a foreboding aspect in the last bits of this study with the researchers explicitly stating that “the large reservoirs of Sars-like viruses found in bats, together with the culture of eating exotic mammals in southern China, is a time bomb” and “the reemergence of SARS and novel viruses from animals or laboratories should not be ignored”.

Although dwelling in the past can seem to be counterintuitive at times, the takeaway here is that we must pay close attention to the scientific literature at present and make all the necessary sacrifices to safeguard our future.

The King’s Hidden Blades

From his home in the east, he has devised offenses that have conquered the human spirit. Through only the piercing eyes of our scholars do his machinations lay bare.

Viewing things from a different perspective can truly give us some unexpected results. Speaking of separate viewpoints, the origin story in itself is twofold. The virus’s key features don't just tell us where the crown came from, it also tells us how it dominated the world. Knowing the enemy’s weapons can reveal its plan of attack. Like two sides of the same coin, we now look at the other end of the virus’ spike proteins, and it points us towards the ACE2 receptors and the enzyme furin.

When a virus enters the human body, its main goal is to find a host cell. It detects these host cells by continuously bumping its spike proteins into the outside receptors of cell membranes until it finds a match. The problem lies in how our bodies handle SARS-CoV-2. In some ways, the situation is quite ironic. Furin is designed to cleave certain proteins to activate them. When furin comes into contact with one of the S spike proteins present in SARS-CoV-2, it helps speed up the host infiltration process by priming the spikes. Once activated, the full receptor-binding domain (RBD) is revealed. These RBDs now hunt for ACE2 receptors found in certain cells.

ACE2 has been a hot target by these SARS-like viruses throughout the years, but one striking difference between each of them is the strength at which they form bonds with the RBDs. Researchers, from the University of Texas and the National Institute of Allergy and Infectious Diseases, have found that SARS-CoV-2 binds 10 to 20 times more tightly to ACE2 when compared to SARS-CoV. On a side note, the reason why SARS-CoV-2 debilitates the respiratory system to such a degree is the high concentrations of both ACE2 and furin within the respiratory tract. It doesn’t end there, a danger lies within the heart of it all.

A study made by Yi Ming and Liu Quiang, from the University of South China, has suggested that the depletion of ACE2 receptors within the cells of the heart can directly affect the processes needed to mediate blood pressure and muscle injury. Even with all its lethal armaments, the virus also contains the element of stealth. Asymptomatic cases have been a serious problem when dealing with person-to-person transmissions. An article within the International Journal of Infectious Diseases has speculated that 20% of all the COVID-19 patients may have been asymptomatic. Studies proposing the inhibition of ACE2 and furin may be promising, but the race continues as we fight this unseen but ever-changing threat.

An Ever-Changing Monarch

As with all tyrannies, the crown never sits on one head for too long. An heir must come to take his rightful prize and continue the corrupt legacy.

Rapid mutation stands as one of the most spine-chilling characteristics a virus possesses. To be able to change their very structure within a short period can be daunting at times. Luckily for us, the literature surrounding the capacity of SARS-CoV-2 to quickly change and adapt has proven to be rather optimistic. From its origins as the novel coronavirus that terrorized Wuhan to its now global presence, not much has changed in its genome.

To put it into perspective, the prevalent strains of today only differ by about 10 nucleotides when compared to the original sample at Wuhan, which was 29,903 nucleotides long. This estimate by Lucy Van Dorp, a geneticist at University College London, lies in the same ballpark with the even lower approximations of 7.23 mutations per sample made by Daniele Mercatelli and Frederico M. Giorgi of the University of Bologna, Italy. Although 10 might not seem much, it is important to know that even the slightest of changes in the genome can spell disaster. As a matter of fact, the most common strain nowadays is characterized by a D614G mutation, a single-letter change within the RNA of the virus’ spike protein.

In an infographic made by the journal Nature, the mutation seems to open up the spike proteins, making the likelihood of binding even higher. This was quite alarming for the researchers who initially discovered its meteoric rise within Europe and Asia. It’s also possible that this variant has already been circulating within the Philippines. The Philippine Genome Center (PGC) has detected such anomalies within the COVID positive samples collected in Quezon City as far back as July.

Many have speculated that this mutation causes increased infectivity and transmissivity, but the literature isn’t that clear. What’s exciting though is the fact that knowing the virus’s minute details gives us ideas on how to deal with it. This could lead to advancements within the development of vaccines by providing steps in creating antibodies.

At Wits’ End

Once again the brightest minds have been brought to their wits’ end. At this very junction do we test the limits of human capability.

The surge of literature surrounding COVID-19 is nothing short of miraculous, and the availability of such materials has never been so direct and accessible. It’s great to see that publications, such as ScienceDirect, have opened up their resources to the public at virtually no cost. Imagine having studies of such caliber available at your fingertips, and it’s just lying there calling out to you. Countless articles have been made by reputable sources to simplify and make the data easy to go through. Media coverage has not lacked one bit to inform the greater public about the current crisis. The World Health Organization (WHO) has been tireless in its attempts to keep track of and address the issues this virus brings. Some have doubted our capability to produce a vaccine as soon as possible, but the reality is that possible treatment may be ready by next year. The New York Times covers, in real-time, the race for the coronavirus vaccine, and based on their count, some vaccines have already been approved for limited use.

Perhaps what lies underneath the crown has already fallen and is a ruler no more. It’s only a matter of time until the crown serves no purpose but a symbol of our triumph. As with all our battles, we have not gone unscathed, but that is the price we must pay. More will come to take its throne, but by that time, we’ll already have the wisdom of facing those who came before them.

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A heritage shrouded in mystery