Just as a tight core is a component of good physical fitness for humans, helping to stabilize our bodies, mutations that tightened the core of the SARS-CoV-2 spike protein in new variants may have increased the virus’s fitness.
“We wanted to see how the spike protein morphed structurally as it evolved from the original wild-type strain of the virus, through the alpha, delta and most recently omicron variants,” said Ganesh Anand, associate professor of chemistry and of biochemistry and molecular biology, Penn State.
“We found that the spike protein was initially more flexible at the stem region, which is where the spike protein is bundled together, but over time, mutations caused the protein to become progressively tighter and more rigid, and we think it’s now as rigid as it can get. This is important because it means that vaccines that are developed to target the current variant with these rigid spike proteins are likely to be effective for much longer than previous vaccines against the more flexible wild-type strain.”
To study how the spike protein changed with each of the new variants, the team studied the virus in vitro (in a test tube) using a technique called amide hydrogen/deuterium exchange mass spectrometry.
Anand explained that the SARS-CoV-2 spike protein is composed of three chain molecules called monomers that are bound together to form a trimer. The spike protein is made up of two subunits, an S1 and S2 subunit. The S1 subunit contains a receptor binding domain while the S2 subunit contains the stem region responsible for bundling the trimer.
“It is analogous to a tree, with the stem forming the trunk and the receptor binding domain forming the branches,” said Anand.
The team’s results, which published in the journal eLife, revealed that the spike protein stem first became more rigid with the D614G mutation, which is common to all SARS-CoV-2 variants. The stem became progressively more twisted with the emergence of new mutations in subsequent variants, and the omicron BA.1 variant showed the largest magnitude increase in stabilization relative to preceding variants.
Why would the virus benefit from a tighter core?
“We did not study the virus in patients, so we cannot determine if the changes we observed in the spike protein directly affected the newer variants such as omicron’s ability to transmit more readily; however, we can say that the changes likely made the virus more fit, which could translate to better transmission,” said Anand.
“A tighter core could likely make the virus more stable in nasal droplets and faster at binding to and entering host cells. So, for example, what initially took about 11 days to develop an infection after exposure now takes only about four days.”
Anand noted that one of the reasons the vaccines have not been able to fully neutralize the virus is because they were generated against the spike protein of the original wild-type variant.
“The latest bivalent booster—which targets newer variants—helps, but people who never got this booster aren’t receiving this more targeted protection,” he said. “Future vaccines that focus specifically on omicron are likely to be effective for longer.”
Finally, Anand said that the spike protein has now become so tightly twisted that it is unlikely to structurally change further at the stem region.
“There are limits to how much it can tighten,” he said. “I think that we can have some cautious optimism, in that we’re not going to continuously have variants emerging, at least tightening is not going to be a mechanism.”
News
Scientists Unlock a New Way to Hear the Brain’s Hidden Language
Scientists can finally hear the brain’s quietest messages—unlocking the hidden code behind how neurons think, decide, and remember. Scientists have created a new protein that can capture the incoming chemical signals received by brain [...]
Does being infected or vaccinated first influence COVID-19 immunity?
A new study analyzing the immune response to COVID-19 in a Catalan cohort of health workers sheds light on an important question: does it matter whether a person was first infected or first vaccinated? [...]
We May Never Know if AI Is Conscious, Says Cambridge Philosopher
As claims about conscious AI grow louder, a Cambridge philosopher argues that we lack the evidence to know whether machines can truly be conscious, let alone morally significant. A philosopher at the University of [...]
AI Helped Scientists Stop a Virus With One Tiny Change
Using AI, researchers identified one tiny molecular interaction that viruses need to infect cells. Disrupting it stopped the virus before infection could begin. Washington State University scientists have uncovered a method to interfere with a key [...]
Deadly Hospital Fungus May Finally Have a Weakness
A deadly, drug-resistant hospital fungus may finally have a weakness—and scientists think they’ve found it. Researchers have identified a genetic process that could open the door to new treatments for a dangerous fungal infection [...]
Fever-Proof Bird Flu Variant Could Fuel the Next Pandemic
Bird flu viruses present a significant risk to humans because they can continue replicating at temperatures higher than a typical fever. Fever is one of the body’s main tools for slowing or stopping viral [...]
What could the future of nanoscience look like?
Society has a lot to thank for nanoscience. From improved health monitoring to reducing the size of electronics, scientists’ ability to delve deeper and better understand chemistry at the nanoscale has opened up numerous [...]
Scientists Melt Cancer’s Hidden “Power Hubs” and Stop Tumor Growth
Researchers discovered that in a rare kidney cancer, RNA builds droplet-like hubs that act as growth control centers inside tumor cells. By engineering a molecular switch to dissolve these hubs, they were able to halt cancer [...]
Platelet-inspired nanoparticles could improve treatment of inflammatory diseases
Scientists have developed platelet-inspired nanoparticles that deliver anti-inflammatory drugs directly to brain-computer interface implants, doubling their effectiveness. Scientists have found a way to improve the performance of brain-computer interface (BCI) electrodes by delivering anti-inflammatory drugs directly [...]
After 150 years, a new chapter in cancer therapy is finally beginning
For decades, researchers have been looking for ways to destroy cancer cells in a targeted manner without further weakening the body. But for many patients whose immune system is severely impaired by chemotherapy or radiation, [...]
Older chemical libraries show promise for fighting resistant strains of COVID-19 virus
SARS‑CoV‑2, the virus that causes COVID-19, continues to mutate, with some newer strains becoming less responsive to current antiviral treatments like Paxlovid. Now, University of California San Diego scientists and an international team of [...]
Lower doses of immunotherapy for skin cancer give better results, study suggests
According to a new study, lower doses of approved immunotherapy for malignant melanoma can give better results against tumors, while reducing side effects. This is reported by researchers at Karolinska Institutet in the Journal of the National [...]
Researchers highlight five pathways through which microplastics can harm the brain
Microplastics could be fueling neurodegenerative diseases like Alzheimer's and Parkinson's, with a new study highlighting five ways microplastics can trigger inflammation and damage in the brain. More than 57 million people live with dementia, [...]
Tiny Metal Nanodots Obliterate Cancer Cells While Largely Sparing Healthy Tissue
Scientists have developed tiny metal-oxide particles that push cancer cells past their stress limits while sparing healthy tissue. An international team led by RMIT University has developed tiny particles called nanodots, crafted from a metallic compound, [...]
Gold Nanoclusters Could Supercharge Quantum Computers
Researchers found that gold “super atoms” can behave like the atoms in top-tier quantum systems—only far easier to scale. These tiny clusters can be customized at the molecular level, offering a powerful, tunable foundation [...]
A single shot of HPV vaccine may be enough to fight cervical cancer, study finds
WASHINGTON -- A single HPV vaccination appears just as effective as two doses at preventing the viral infection that causes cervical cancer, researchers reported Wednesday. HPV, or human papillomavirus, is very common and spread [...]
