ROCHESTER, Minn. -- It's become the most recognizable tangle of molecular ribbon in the world.
Otherwise known among molecular scientists as spike, it is a protein sticking out of the virus that causes COVID-19.
As anyone who has seen the drawings can tell you, the crown-like spikes adorning SARS-CoV2 look like suction cups protruding from a beach ball That's in the COVID-19 cartoons anyway.
In the higher-grade artwork, spike flowers upward like small heads of broccoli. Seen up close, spike looks more like a tapered cluster of grapes, or blooms of sea coral riding a knotty stem upward into a mushroom-shaped head.
Zoom in closer than that, and spike looks like a tangled nest of bands.
It all seems sort of benign, and yet spike has brought the world to a halt. So, what exactly is spike? How exactly does it hurt us? And if spike is so bad, isn't shooting genetic plans on how to make them into our arms a recipe for trouble?
They're all important questions, because as it turns out, everything we care about when it comes to COVID-19 -- how it makes us sick and what can be done to prevent the next coronavirus to jump from bats into humans, has come down to our surprising new understanding of spike.
More than just a suction cup
At the beginning of the outbreak, spike was portrayed as little more than the docking mechanism on a spaceship.
In this telling of the COVID-19 transmission story, after breathing in someone's infected aerosols, virus studded with spike bounced along the recipient's airways en route to a location capable of receiving its genetic payload.
These spike-docking stations were eventually identified by scientists as the so-called angiotensin-converting enzyme, or ACE2 receptors, chemical portals for enzymes regulating dilation and constriction of the blood vessels.
ACE2 receptors are located throughout the body, but in this case, the ones opening the doorway for COVID-19 were in endothelial cells lining the alveoli and arteries of the lungs. ACE2 receptors also line the mouth and the nose and are greater in number among those who smoke.
The fact that these ACE2 receptors proliferate in patients with diabetes and hypertension could explain the worse outcome for people with those conditions. They have more loading docks for receiving spike.
Spike sees these ACE2 receptors and latches on to them like a key that finally bumps into its lock. When that happens, SARS-CoV-2 takes over the endothelial cell's machinery and begins producing millions of copies of itself.
Although ACE2 receptors are found in distant organs of the body (including the heart, kidneys and intestine), this first layover in the lungs and airways for COVID-19 replication led scientists to view the virus like pneumonia or bronchitis.
"A lot of people think of it as a respiratory disease, but it's really a vascular disease," is how Uri Manor, a researcher at the Salk Institute in California, described this misunderstanding last month.
His comments were given to accompany a study that established for the very first time that COVID-19 is first and foremost a disease of the blood supply, as opposed to the lungs, and an illness driven not so much by the proliferation of virus but the harmful effects of, you guessed it, spike.
It proved this by giving animals and then human endothelial cells something very close to COVID-19 the illness, without ever giving them SARS-CoV-2 the virus. How? By giving them a fake virus, covered in spike.
The researchers learned that in binding nothing but spike to ACE2, it interfered with the receptors' effects on mitochondria, the engine rooms of the body's vascular system, and those then became damaged.
Watch out for that stalk
When we thought of spike as a mere set of landing gear, we used to think the body fought off COVID-19 by jamming the head of the spike -- the part that docks with ACE2 receptors.
Scientists believed our antibodies produced in response to the virus blocked that interface at the so-called Receptor-Binding Domain (RBD), an acronym for the real estate at the very top of these crowns.
But that was more of the same, simplistic space-station thinking about COVID-19.
"We found these antibodies are painting the entire spike, both the arc and stalk of the spike protein, which looks a bit like an umbrella," said Greg Ippolito, a researcher at the University of Texas. He offered that comment in a statement accompanying research earlier this month, work that showed nearly half of the antibodies that target spike -- 40% -- go after a portion of the stalk and fortunately a part of the virus that doesn't mutate easily.
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Their goal today is to find a single vaccine that can prevent every coronavirus still to mutate or emerge from the kingdom of bats and other wildlife. That vaccine -- a "pan coronavirus vaccine" -- is inching closer to reality.
New findings from Scripps Research is showing that when you take spikes from many different coronaviruses, hit them all with antibodies and look at them individually under the microscope, you eventually find a section of the spike common to every coronavirus.
Find a vaccine that draws antibodies targeting the universal part of spike and you find a vaccine that prevents COVID-19 for a lifetime, with the caveat that it's hard to know a vaccine protects against a virus that has not been created. Dozens of labs around the world are now trying to create just such a vaccine.
Won't sending spike instructions into our arms harm us?
If spike is so dangerous, doesn't giving ourselves a vaccine that causes the body to make more of them seem like a bad idea? How come getting vaccinated with an mRNA vaccine doesn't make us worse?
It turns out, spikes from COVID-19 infections go to one place (the blood supply), while spikes created from an mRNA vaccine, limited in number, stay on the cells in the muscle tissue of your shoulder and nearby lymph system -- site of the body's immune response.
As Derek Lowe, a columnist for Science Magazine recently reported, the spike created from vaccination doesn't find any ACE2 receptors either, allowing the vaccine to damage the mitochondria as found in connection to contagious forms of spike.
Errant vaccine-created spikes that do enter the blood supply after vaccination are destroyed by enzymes in the liver. Research shows just 1% of the vaccine-created spikes ended up elsewhere in the body.
To recap, it was once believed that spike was little more than a connector, that COVID-19-related harm was carried out in the lungs, and that the future of prevention lay in attacking that connection process.
We have learned since that all three of those ideas are wrong, and that Spike has an achilles heel. As a result, we are closer than ever to developing a vaccine that can stop every coronavirus that ever comes out a bat again.
Coming up next this series: The future of COVID-19, Part 2: The 4 drugs proven to work (and 2 that remain unproven).