Coronavirus: Know the enemy

Covid – or any other foe – is best beaten with fact-based strategy, not rumor. So wade right in…

Nikhil Menon

In many cases, the new coronavirus has us either hunkered down, doing krav maga poses to fend off others inept at social distancing, or clambering up the supermarket shelves for that forlorn bottle of hand soap that could save us from the apocalypse. You know? Panic.

Sometimes it may be better to face your fears, ergo the injunction that is the title of our piece.

If you know the disease called COVID-19 (short for coronavirus disease 2019), you will know what it does, the risk it poses – and does not – and how to deal with it.

By the end of this piece, we expect you will come out calmer, more informed, and with a canny strategy to face the virus.

The skinny on viruses

First up, a virus is not some malevolent predator out to get you. Leave alone some super villain, it is not even alive in the conventional sense. It is just a little wrapped-up genetic material set on autopilot to multiply as long as it finds the suitable resources in a host (for example, a bat). Else, it degrades and crumbles away.

Over time, thanks to small accidental genetic changes, these viruses change how they work. Most of them cannot survive these errors. But sometimes an “error” gives it an accidental advantage, letting it survive in a new host (such as a human) better than their ancestors. Our own DNA consists of 5-8% of viral material, with some being expressed as early as when we are fetuses. Just like bacteria, most viruses are harmless to us. Some viruses have also been used to fight dangerous bacteria.

It does not help for the viruses to be lethal too fast. Those that kill the golden goose – or, more relevantly, human – are less likely to survive, having killed their source of raw material. That is why viruses that happen to stick around for centuries do damage slowly to the host. Case in point, the common cold.

Past as prologue

Viruses have been infecting humans for centuries. Textbooks of basic virology, including one called, well, Basic Virology, discuss archaeological evidence from Egyptian mummies and medical texts of the time that in lurid detail discuss such virus-caused problems as warts (genital papillomas) and polio (caused by the eponymous microbe).

The Middle Ages were plagued with smallpox epidemics that wiped out whole communities of people, subsequent European conquests generously spreading diseases such as measles around the world. The ‘Spanish’ influenza of 1918-19, a frequent point of reference for today’s discussion of COVID-19, moved from birds to humans, to kill tens of millions of people worldwide. In 2005, a similar virus (H5N1), which also moved from birds to humans, sparked panic. But since human-to-human transmission was extremely rare, H5N1 was potentially less dangerous.

The current wave of coronaviruses spanning the globe is not the first one we know of. Recent ones include SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). For the most part, coronaviruses cause disease in one species. The trouble is when the virus manages to move over to another species. Thanks to some interesting work by Shi Zhengli, there is evidence that SARS found cozy hosts in bats. MERS came from camels and appear to have gone back to roost among them.

Fenner’s Veterinary Virology assures us that the relevant coronovirus subfamily for us is Coronaviridae, which includes viruses for “a remarkable variety of diseases, including pneumonia, reproductive disease, enteritis, polyserositis, sialodacryoadenitis, hepatitis, encephalomyelitis, nephritis, and various other disorders.”

To complete the happy thought, the current virus that has gained our interest is just one of a billion kinds of microbial shocks human flesh is heir to.

Meet our latest microfoe

SARS-CoV-2 (which is what the current version is called) is very similar to two other members of the betacoronavirus family (You may be comforted to know there are three other related families, from the alphacoronaviruses to the deltacoronaviruses). The other two members are SARS-Cov Tor2, an airborne coronavirus associated with respiratory problems in humans, and SL-CoVZC45, a coronavirus that apparently moved from bats to humans, though such transmission has never really been established.

Coronaviruses get their names from the spikes protruding from the membrane surrounding them. This membrane, the viral envelope is made up of a fatty layer studded with some proteins, including the larger spikes that, under the microscope, look like hazy crowns. Ergo, “corona,” or crown.

These spikes are S proteins, masses of glucose and protein (aka glycoproteins) that have various functions, including helping the virus break and enter into human cells, wherein they go forth and multiply.

Initially, like in the case of SARS in 2002, the virus plugs into angiotensin converting enzyme 2 (ACE2), a zinc-powered cell-surface enzyme that, among other things, keeps blood pressure down. ACE2 has been shown to protect mice from some forms of lung injury, since damage to these receptors have been linked to corresponding damage in the lungs.

But the S protein in the new coronavirus is 10 to 20 times more likely to bind to ACE2 than the one seen in the SARS virus of 2002. Researchers from the National Institute of Health and Jason McLellan of the University of Texas at Austin, who made the discovery, also pointed out that three antibodies against the 2002 SARS virus did not work against SARS-CoV-2 spike protein, our current nemesis. This means vaccines and antibody-based treatments that worked with SARS will not work against this one.

Another protein enzyme that spans the membrane, TMPRSS2 (transmembrane protease serine 2) also preps the S protein for the work ahead.

Breakthrough

Once the virus is anchored, its fatty membrane fuses with the cell membrane of the host cell, squirting its RNA – the virus’s genetic material – into the cell. The invader now uses the cell’s raw materials to form new viruses. Its nucleocapsid protein, or “N protein,” is vital for this process.

Besides, there are membrane proteins or “M proteins,” which act as luggage tags, helping us identify the different varieties of the virus, and the envelop proteins, or “E proteins,” which may play roles in managing the virus’s entry into the host cell, and then putting together and releasing the new viruses generated.

This repetitive cycle of attachment, invasion and release is how the virus ducks and weaves, avoiding detection from the immune response.

WHO’s afraid of COVID-19?

We have dealt with coronaviruses before. Some even cause the common cold. So what makes SARS-CoV-2 such a big deal?

Well, despite comparisons being made to the flu, the new coronavirus spreads far faster. For every hundred people infected with the flu, the disease spreads to 30 more people. In the case of SARS-CoV-2, a hundred people can pass it on to about 240 others. Consider that in the infamous 1918 “Spanish flu,” the corresponding number was 150, and for Ebola, 200.

Researchers describe this in terms of a “basic reproduction number” (R0 in the jargon). It is 1.3 for coronavirus, 3.4 for the 2002 SARS virus, etc.

So does a high R0 mean the disease is lethal? Simply put, no. It only helps explains how contagious it is, how fast it travels, and not the risk of death or disability.

Measles has an R0 of 12 to 18, which means it is extremely contagious, but the fatality rate is 15%, Meanwhile, the 2005 Marburg virus, with a fatality rate of more than 80%, had an R0 of about 1.6.

For more details about a comparison between COVID-19 with the flu, ProPublica has a great piece.

So just because some germs spread faster does not mean they kill a larger number of people. SARS-CoV-2 was estimated to have a fatality rate of between 2% and 3% (though even that number is being revised downward). The team at the WHO Collaborating Centre for Infectious Disease Epidemiology and Control at the University of Hong Kong concluded that the risk of fatality is 1.4% for those over 15 years of age, the people most likely to be affected. For those who want the details, the average risk was 0.5% for those between 15 and 64; and 2.7% for those over 64 years of age, who are more at risk for a variety of reasons.

The soapy solution

Sometimes a microbe mutates enough to survive the medicines that worked against its cousins. Then prevention becomes even more important.

In the case of the SARS-CoV-2, the methods suggested are hand-washing, keeping one’s hands off one’s face, and keeping at least six feet away from other people.

Why wash? Well, if you remember what we mentioned a few paras up there, the genetic material in the virus is protected by a fatty membrane.

One side of any fat – such as cooking oil – bonds with water; the other side absolutely avoids it. Our cell membranes – and those found in the coronavirus – are made up of two sandwiched layers, in which the anti-water (or hydrophobic) side faces inward.

Now soaps contain fat-like substances called amphiphiles. Mix soap with water and the hydrophobic side of amphiphiles tend to plug themselves into the nearest available fat – in this case the unfortunate virus on our hands.

The amphiphiles burrow into the virus membrane to get to a suitably hospitable area that is hydrophobic. As you may have guessed, it is not good for the coronavirus to have a load of weird wannabe fats nosing aside bits of its well-structured protective layer, thus breaking it apart. Bad for the virus, of course, not so much for the potential host.

Hand sanitizers often contain alcohol, which thins fat layers and make them leaky. It also wreaks havoc with the proteins, damaging them often beyond repair. According to the Center for Disease Control, the sanitizer needs to be at least 60 percent alcohol. Remember, it is not as effective as soap and water for those really grimly hands.

Given that between washes, you may have accidentally touched some inoffensive-looking surface that offered temporary refuge to a homeless virus, it is also recommended that you avoid pawing your own face.

Keep your distance!

Then there is the social distancing option. Even after keeping your hands clean, off other people, surfaces that may be infected, and one’s own mug, the virus still has one more option: direct flight over to you.

Since it takes about two weeks from the initial symptoms showing up to full-blown COVID-19, infected people can move around handing out the virus, literally or figuratively. One of the symptoms of the disease is a cough, which sprays the surrounding area with small droplets of virus-laden fluid.

Though these droplets may start out as fast as 100 mph (160kmph), like a balloon that’s been hit hard, they quickly slow down in the face of air resistance. Most of these hit the floor within six feet, but a group at MIT found out that the smaller droplets, eddying around as one shoots them out the snoot, can not only travel up to 26 feet, but, being light, also rise. The smallest droplets, 10 micrometers wide, can go much, much, much farther… Of course, the tinier droplets have a much smaller payload of virus and so pose less risk.

The experts have concluded that about six feet is enough to keep most people safe from most of the danger posed. This, they believe, will slow the spread of the virus and reduce the number of people infected over time.

A recent Washington Post article (soft paywall) compares the differences between an attempted quarantine, moderate distancing and extensive distancing on COVID-19 infection. Extensive distancing was the clear winner, with a significantly smaller portion of the population being infected.

Social isolation has been shown to “flatten the curve” of the number of people infected.

The twilight zone

There are rumors that warmer weather can slow the progress of COVID-19 since hot surfaces can wreck the viral machinery. Well … not quite. Australia, with the temperature up at 70 degrees F (20 degrees C), is dealing with it. So is Saudi Arabia.

The disease is too new for people to have immunity yet, or for vaccine or suitable antiviral to be developed. The current flu vaccine is certainly ineffective since it lacks the kind of proteins that will make an antibody perk up its metaphorical ears and draw the immune system’s attention to the danger.

The road ahead

According to the Guardian, about 35 companies and academic intuitions are working on vaccines, at least four of whom have juicy candidates ready for animal testing.

Labs tend to work with mice, not bats or pangolins, which seem to be happy hunting grounds for SARS-CoV-2. This delays testing, at least until susceptible rodents are bred to serve as model organisms to test vaccines on.

One research lab has decided that since their vaccine works in concept, they can skip the animal testing phase and move quickly to human trials. While this has naturally caused some murmurs in the research community, there may be less pushback because the benefits may be seen to outweigh the risk. After all, one experienced researcher concluded 60 percent of the world’s population could get the infection. That’s about 4.6 billion people. It could cause economic, political and, yes, perhaps even gastrointestinal upheavals.

So, just for the sake of the planet, wash your hands every which way you can, and just, please, keep six feet away.

Nikhil Menon is a PhD candidate student at Texas Tech University. He studies the neuroendocrinology of hyperglycemia in anxiety disorders.

With inputs from P Rajendran