The COVID-19 pandemic has prompted considerable investigation into how the SARS-CoV-2 Spike protein attaches to a human cell during the infection process, as this knowledge is useful in designing vaccines and therapeutics. Now, a team of scientists has discovered additional locations on the Spike protein that may not only help to explain how certain mutations make emerging variants more infectious but also could be used as additional targets for therapeutic intervention.
“Significant research is underway to examine how the receptor binding domain (RBD) at the tip of the club-shaped SARS-CoV-2 Spike protein attaches to an ACE2 receptor on a human cell, but little is known about the other changes that occur in the Spike protein as a result of this attachment,” said Ganesh Anand, associate professor of chemistry, Penn State. “We have uncovered ‘hotspots’ further down on the Spike protein that are critical for SARS-CoV-2 infection and may be novel targets beyond the RBD for therapeutic intervention.”
Anand and his colleagues used a process, called amide hydrogen-deuterium exchange mass spectrometry (HDXMS), to visualize what happens when the SARS-CoV-2 Spike protein binds to an ACE2 receptor. HDXMS uses heavy water or deuterium oxide (D2O), a naturally occurring, non-radioactive isotope of water formed from heavy hydrogen or deuterium, as a probe for mapping proteins. In this case, the team placed SARS-CoV-2 Spike protein and ACE2 receptors in heavy water and obtained footprints of ACE2 on the Spike protein.
“If you put the Spike protein and ACE2 receptor into a solution that’s made with D2O, the surfaces and more floppy regions on both proteins will more readily exchange hydrogens for deuterium, compared to their interiors,” said Anand. “And footprints of each protein on the binding partner can be readily identified from areas where you see little deuterium and only detect normal hydrogen.”
Using this technique, the team determined that binding of the Spike protein and ACE2 receptor is necessary for furin-like proteases—a family of human enzymes—that act to snip off the tip, called the S1 subunit, of the Spike protein, which is the next step in the virus’s infection of the cell. The findings published on Feb. 8 in the journal eLife.
Image Credit: NIH/NIAID
Post by Amanda Scott, NA CEO. Follow her on twitter @tantriclens
Thanks to Heinz V. Hoenen. Follow him on twitter: @HeinzVHoenen
News
Signs of Multiple Sclerosis Show Up in Blood Years Before Symptoms Appear
UCSF scientists clear a potential path toward earlier treatment for a disease that affects nearly 1,000,000 people in the United States. By Levi Gadye In a discovery that could hasten treatment for patients with multiple [...]
Advanced RNA Sequencing Reveals the Drivers of New COVID Variants
A study reveals that a new sequencing technique, tARC-seq, can accurately track mutations in SARS-CoV-2, providing insights into the rapid evolution and variant development of the virus. The SARS-CoV-2 virus that causes COVID has the unsettling [...]
No More Endless Boosters? Scientists Develop One-for-All Virus Vaccine
End of the line for endless boosters? Researchers at UC Riverside have developed a new vaccine approach using RNA that is effective against any strain of a virus and can be used safely even by babies or the immunocompromised. Every [...]
How Are Hydrogels Shaping the Future of Biomedicine?
Hydrogels have gained widespread recognition and utilization in biomedical engineering, with their applications dating back to the 1960s when they were first used in contact lens production. Hydrogels are distinguished from other biomaterials in [...]
Nanovials method for immune cell screening uncovers receptors that target prostate cancer
A recent UCLA study demonstrates a new process for screening T cells, part of the body's natural defenses, for characteristics vital to the success of cell-based treatments. The method filters T cells based on [...]
New Research Reveals That Your Sense of Smell May Be Smarter Than You Think
A new study published in the Journal of Neuroscience indicates that the sense of smell is significantly influenced by cues from other senses, whereas the senses of sight and hearing are much less affected. A popular [...]
Deadly bacteria show thirst for human blood: the phenomenon of bacterial vampirism
Some of the world's deadliest bacteria seek out and feed on human blood, a newly-discovered phenomenon researchers are calling "bacterial vampirism." A team led by Washington State University researchers has found the bacteria are [...]
Organ Architects: The Remarkable Cells Shaping Our Development
Finding your way through the winding streets of certain cities can be a real challenge without a map. To orient ourselves, we rely on a variety of information, including digital maps on our phones, [...]
Novel hydrogel removes microplastics from water
Microplastics pose a great threat to human health. These tiny plastic debris can enter our bodies through the water we drink and increase the risk of illnesses. They are also an environmental hazard; found [...]
Researchers Discover New Origin of Deep Brain Waves
Understanding hippocampal activity could improve sleep and cognition therapies. Researchers from the University of California, Irvine’s biomedical engineering department have discovered a new origin for two essential brain waves—slow waves and sleep spindles—that are critical for [...]
The Lifelong Cost of Surviving COVID: Scientists Uncover Long-Term Effects
Many of the individuals released to long-term acute care facilities suffered from conditions that lasted for over a year. Researchers at UC San Francisco studied COVID-19 patients in the United States who survived some of the longest and [...]
Previously Unknown Rogue Immune Key to Chronic Viral Infections Discovered
Scientists discovered a previously unidentified rogue immune cell linked to poor antibody responses in chronic viral infections. Australian researchers have discovered a previously unknown rogue immune cell that can cause poor antibody responses in [...]
Nature’s Betrayal: Unmasking Lead Lurking in Herbal Medicine
A case of lead poisoning due to Ayurvedic medicine use demonstrates the importance of patient history in diagnosis and the need for public health collaboration to prevent similar risks. An article in CMAJ (Canadian Medical Association [...]
Frozen in Time: How a DNA Anomaly Misled Scientists for Centuries
An enormous meteor spelled doom for most dinosaurs 65 million years ago. But not all. In the aftermath of the extinction event, birds — technically dinosaurs themselves — flourished. Scientists have spent centuries trying [...]
‘Mini kidneys’ reveal new insights into metabolic defects in polycystic kidney disease
Scientists at Nanyang Technological University, Singapore (NTU Singapore) have successfully grown 'mini kidneys' in the lab and grafted them into live mice, revealing new insights into the metabolic defects and a potential therapy for [...]
Decoding the Origin of Life: Scientists Solve Early Earth RNA Puzzle
Recent research illustrates how RNA molecules’ chemical characteristics might have played a crucial role in the development of complex life forms. How did complex life manage to evolve on the early, inhospitable Earth? Initially, [...]