MAR 17, 2020 5:38 AM PDT

What's the deal with SARS-CoV-2's spike protein?

WRITTEN BY: Tara Fernandez

Structurally, SARS-CoV-2 (the viruses that cause COVID-19) are spherical shells made up of a lipid membrane, with a core containing the virus’ genetic material. This genetic information on its own is not enough for the virus to replicate. For this, it needs to first infect a living cell.

Intense vaccine development efforts are currently underway, with many programs focused on priming the immune system against a specific protein on the surface of SARS-CoV-2, known as the spike protein. These protein projections protruding from the surface of the virus give it a “crown-like” appearance and have been found to help it to infiltrate human cells.

During infection, the spike protein acts as a key, binding to receptors on human cells in a process that is activated by enzymes present on the host cell. This enzyme-mediated process “unlocks” cells and allows the virus to gain entry, where it then hijacks the cell’s machinery to replicate. 

Interestingly, while other coronaviruses also bear spike proteins, emerging genomic analysis has revealed some unique features of those present on SARS-CoV-2. Researchers have identified that COVID-19 infections occur as a result of spike proteins that have been activated by a particular host-cell enzyme called furin. Significantly, furin is not only present on lung cells, but also in the tissues of the liver and small intestine, giving SARS-CoV-2 multiple potential entry points into the human body. Scientists have attributed liver failure in some COVID-19 patients to this particular characteristic.

Other researchers believe that this special furin activation site could also affect the virus’ stability, pathogenicity and mode of transmission, enabling the rapid spread of infection between individuals.

However, when it comes to relating SARS-CoV-2’s distinctive spike protein to its infectivity, not all scientists see eye to eye. Researchers have not yet mapped the precise molecular pathways occurring during viral entry, nor do they fully understand how the virus’ activation sites correlate with its virulence. While comparing SARS-CoV-2's structural components to that of other SARS viruses may offer some clues, it remains challenging to draw solid conclusions. For example, the influenza virus, which does not have a furin activation site, was responsible for the deadliest recorded pandemic, the Spanish flu of 1918.

The receptor on human cells that the spike protein attaches to is called angiotensin-converting enzyme 2 (ACE2), with this attachment being facilitated by the spike protein's furin activation site. The binding of SARS-CoV-2 to this receptor is at least ten times stronger than that of other SARS viruses, which may be an important factor influencing COVID-19 transmission rates. As an alternative to vaccines that target the spike protein, scientists predict that other therapeutic strategies could also be effective, such as temporarily blocking ACE2 in cells to prevent the entry of the virus.

Presently, the SARS-CoV-2 spike protein is being heavily used as a target antigen in vaccine development. It serves as a unique molecular identifier that the immune system will “remember” to resist COVID-19 infection. At the same time, scientists like Gary Whittaker, a virologist at Cornell University, continue to delve into the intricacies around exactly how the spike protein infects human cells so well. By removing or modifying specific sites on the protein, the research team is studying how the protein’s sequence relates to viral infectivity. Understanding the spike protein’s role in the context of the COVID-19 pandemic is no easy feat, considering so much has yet to be discovered about the biology of this newly emerged virus. According to Whittaker, “Coronaviruses are unpredictable, and good hypotheses often turn out to be wrong.”

 


Sources: Nature, The Harvard Gazette.

About the Author
  • Tara Fernandez has a PhD in Cell Biology and has spent over a decade uncovering the molecular basis of diseases ranging from skin cancer to obesity and diabetes. She currently works on developing and marketing disruptive new technologies in the biotechnology industry. Her areas of interest include innovation in molecular diagnostics, cell therapies, and immunology. She actively participates in various science communication and public engagement initiatives to promote STEM in the community.
You May Also Like
JUN 25, 2020
Immunology
The Protein That Orchestrates Cells' Dance of Death
JUN 25, 2020
The Protein That Orchestrates Cells' Dance of Death
When cells become diseased or infected, a “suicide switch” is triggered, preventing neighboring cells from b ...
JUL 07, 2020
Immunology
Existing drugs can prevent SARS-CoV-2 from hijacking cells
JUL 07, 2020
Existing drugs can prevent SARS-CoV-2 from hijacking cells
An international team of researchers has analysed how SARS-CoV-2, the virus that causes COVID-19, hijacks the proteins i ...
JUL 14, 2020
Coronavirus
What Makes A Strong Antibody Response to Coronavirus
JUL 14, 2020
What Makes A Strong Antibody Response to Coronavirus
Scientists all over the world are racing to develop a vaccine that effectively and safely prompts protective immunity to ...
JUL 21, 2020
Immunology
Hormone Therapies Keep Urinary Tract Infections at Bay
JUL 21, 2020
Hormone Therapies Keep Urinary Tract Infections at Bay
More than half of all women will suffer from a urinary tract infection, or UTI, during their lifetimes. Women are consid ...
AUG 18, 2020
Immunology
How Dolphins Could Help Us Live Longer
AUG 18, 2020
How Dolphins Could Help Us Live Longer
Dolphins are helping scientists answer the age-old question: can we stop the clock when it comes to aging? A recent stud ...
OCT 12, 2020
Drug Discovery & Development
Researchers Solve Key Problem for Cancer Immunotherapy
OCT 12, 2020
Researchers Solve Key Problem for Cancer Immunotherapy
Cancer immunotherapies are becoming increasingly promising as a standard-of-care treatment. However, despite their promi ...
Loading Comments...