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
JUL 12, 2021
Cell & Molecular Biology
A Molecule From the Gut Microbiome May Fight Tumors
JUL 12, 2021
A Molecule From the Gut Microbiome May Fight Tumors
The more we learn abut the gut microbiome, the more it seems that the microorganisms in our gastrointestinal tracts can ...
JUL 20, 2021
Immunology
Coronavirus Variants No Match Against Newly-Discovered Antibody
JUL 20, 2021
Coronavirus Variants No Match Against Newly-Discovered Antibody
Over 940 million people around the world have been fully vaccinated. But, as the World Health Organization warns, t ...
JUL 29, 2021
Drug Discovery & Development
What is Ivermectin and Can it Treat COVID?
JUL 29, 2021
What is Ivermectin and Can it Treat COVID?
Lab tests in 2020 found that the widely available drug ivermectin had a weak effect on the SARS-CoV-2 virus and that unf ...
JUL 30, 2021
Cancer
Obesity Reduces Mortality in Advanced Prostate Cancer
JUL 30, 2021
Obesity Reduces Mortality in Advanced Prostate Cancer
Obese patients with an advanced form of prostate cancer survive longer than their slimmer counterparts, according to res ...
AUG 10, 2021
Health & Medicine
Care Managers During COVID-19, A Vital Value-Add
AUG 10, 2021
Care Managers During COVID-19, A Vital Value-Add
At the beginning of 2020, fear was unleashed globally as the United States government announced a public health emergenc ...
AUG 27, 2021
Health & Medicine
Blood Group and COVID-19 Susceptibility- An Ongoing Debate
AUG 27, 2021
Blood Group and COVID-19 Susceptibility- An Ongoing Debate
Since their discovery, there has been an interest in how ABO blood groups and infectious diseases may be related. In add ...
Loading Comments...