At this stage of the pandemic, the structure of SARS-CoV-2 – the virus that causes Covid-19 – is cemented in most of our brains. Imagine a small atmosphere covered with narrow-minded spikes.
These spike proteins, which support the surface of the virus, are notorious for their ability to attach to human cell receptors called ACE2, allowing the virus to efficiently enter human cells and cause destruction on the body.
But while spike proteins get a deservedly bad wrap, they also offer a chance to stop Covid-19 infections before they begin.
Compared to fighting infection when the virus is already in the body, preventing the spike-protein-ACE2 interaction is relatively simple, researchers say. Ultimately, it could be a more effective approach.
The process of how the virus goes from hooking up and entering a cell to becoming an infection that leads to you becoming ill and infected is “very complex”, says Stephen Goldstein, an evolutionary virologist who studies coronaviruses at Utah University Health. He tells Inverse that the easiest way, in theory, is to interrupt that process to prevent the virus from attaching or entering in the first place.
By targeting the spike protein, you can hopefully interfere with that first step, which, while not very simple, has the potential to be much simpler than going through all the complicated processes that occur after the virus enters a cell, “Goldstein explains.
Goldstein compares this approach to combating a home invader.
“When someone comes up to rob your house, the simplest way to prevent your door is to be locked, right?” Goldstein says. “If your door is open, and then they come in, then you might have to chase them through the house to stop them from doing what they do. If you just lock your door, they can not even enter.”
Scientists are still finding the best way to drive interference between spike proteins and ACE2 receptors, the key areas by which the virus kills and infects human cells. But new research, on monoclonal antibodies, plasma recovery time, and polybasic cleavage sites suggests that we are getting closer to utilizing spike proteins to our advantage.
Which part of the Covid-19 pandemic do you think causes the most confusion? We want to know. Take the Inverse reader survey.
What is the coronavirus spike protein?
While an outbreak of the magnitude and extent of the Covid-19 pandemic had been predicted for years, experts were not yet intimately aware of the specific behavior and structural dynamics of SARS-CoV-2 when it appeared.
To deal with this previously unknown virus that is circulating through the world population through velocity, scientists jumped to track its viral structure. Thanks to structural similarities with its cousin virus, SARS-CoV, researchers have relatively quickly established the mechanics of the new coronavirus.
They rely on spike protein as a crucial target for diagnosis and therapy. This is because the spike protein, like S-protein, facilitates viral entry into host cells.
Past research on SARS[-CoV] have allowed us to understand how this virus almost infects cells, “says Goldstein. He notes that there are still many that we do not know about the Covid-19 virus, but these structural foundations are understood by scientists of how the virus behaves.
“It was very clear, based on the similarity between the sequence of this spike protein and the spike protein of the original SARS virus, that this virus probably used ACE2 as a receptor,” Goldstein explains.
After the spike protein attaches to the ACE2 receptor, the viral and human membranes fuse. This fusion provides an opening for the virus to invade human cells and begin to infect a person’s body.
Once inside the viral genome, a complex, rapid process of viral replication kicks off. In turn, the immune system is sent into action, producing antibodies and immune cells to fight the infection.
According to scientists, if we can take down viral intruders before we get in the door, we can stop Covid-19 infections before they start. And we can contain the pandemic more effectively.
How to stop an infection before it starts – In a new study, scientists stepped closer to creating a therapy that acts as a Covid-19 bouncer. This study was published August 2 in the journal ACS Nano.
After analyzing the cellular and molecular dynamics of the virus, researchers determined a weak spot of the viral structure – just 10 nanometers away from the binding site of the spike protein. This spicy but pivotal location is positively charged, allowing strong binding between the virus protein and negatively charged human cell receptors.
The study team subsequently designed a negatively charged molecule to bind to the positively charged site, also known as a cleavage site. Blocking this site prevents the virus from binding to the host cell.
Study co-author Monica Olvera de la Cruz, a researcher at the Northwestern McCormick School of Engineering, tells Inverse that blocking this cleavage site could act as a viable prophylactic treatment that reduces the virus’ ability to infect humans.
“It would be a very easy, targeted site if you want to block it,” says Olvera de la Cruz.
She also warns that we are still many studies away from developing a treatment that takes this therapy from theory to practical use.
“We’re looking at something that might be accepted,” Olvera de la Cruz explains. “Yet there is still a long way to go to prove it.”
Commenting on this new study, Goldstein agrees that one “could think of the spike ACE2 interaction as a weak spot.”
It’s conceptually pretty simple about how you would prevent infection by targeting this interaction, he reasons – “but I don’t think this group found it.”
Is there a link between spike proteins and coronavirus mutations?
Recent reports describe a highly infected strain of the coronavirus called D614G that is floating around the world.
Olvera de la Cruz says her team’s results help “experimental research showing that mutations in the SARS-CoV-2 spike protein affect the transmissibility of viruses.”
Goldstein acknowledges that there is “some evidence” that this new variant of Covid-19, D614G, may affect the virus’ ability to infect cells and how efficiently they prevent this process. But it is too early to say for sure.
“We do not yet have clear evidence that it is more transferable,” Goldstein says. “There is certainly no evidence that it is more deadly.” But no matter how interesting it may be that mutations may be at play, Goldenstein notes that mutation-as-not, the possibility does not change “what needs to be done to contain the outbreak.”
“Behavior of humans and how they go about their lives, and how they think about the path through this need not change at all based on what they might read about these interesting scientific questions regarding mutations in the spike protein, he claims.
The spike protein mutations that soe be “immediately concerned,” Goldstein says, are those who would not make monoclonal antibodies effective as vaccines. But there is no evidence of mutations causing this unusual outcome.
Future spike-protein coupled therapies – The spike protein remains a crucial target of attack. However, the best form of attack is uncertain.
In labs around the world, scientists like Olvera de la Cruz also aim to neutralize the spike protein ACE2. Perhaps approaches are through:
Both of these potential therapies, which have not completed researched threads showing that they are safe or effective on a large scale, affect the spike-protein-ACE2 interaction. The better we understand the spike protein and the ability to infect, the closer we will be to an effective treatment for Covid-19.
