The third way! The essential difference between SARS-CoV-2 and SARS

Dr.
Marceline Côté's team at the University of Ottawa has discovered a new entry point for the SARS-CoV-2 virus and suggests that it may be able to use the protein to infect a wider range of cells
.

During the ongoing COVID-19 pandemic, one of the many urgent research tasks in the scientific community is to study how coronaviruses enter host cells
.

Now, in a study, Marceline Côté's lab and collaborators have published a very compelling study showing a previously unidentified entry route to SARS-CoV-2, a virus that causes COVID-19 and is also the driver of the global health crisis that has changed the world
.

Previous studies have shown that SARS-CoV-2, and the early coronavirus SARS-CoV-1, behind the 2003 SARS outbreak, entered cells
through two different pathways.
The new study, led by Dr.
Côté's lab, shows a third pathway
.

This viral entry pathway involves metalloproteinases, which have catalytic mechanisms in the body that require metals such as zinc atoms to function
.

Starting in 2020, Dr.
Côté's research team conducted a series of experiments and found that SARS-COV-2 can enter cells
in a metalloproteinase-dependent manner.
The team described the role of
two matrix metalloproteinases, MMP-2 and MMP-9, in the activation of spike glycoprotein.

What are the consequences of this virality? The study, published in a recent issue of iScience, an open-access journal of Cell Press, suggests that variants that favor metalloproteases could cause more damage
.

The team's experiments showed that some variants significantly prefer the activation
of metalloproteinases.
For example, a more pathogenic Delta variant that surged in 2021 often enters using
metalloproteases.
Its less pathogenic successor, Omicron, did not
.

Dr Côté, Associate Professor in the College of Molecular Virology and Antiviral Therapeutics Research Chair in Canada, said: "SARS-CoV-2 may be able to cause greater damage using proteins, usually secreted by some activated immune cells, and may infect a wider range of cells and tissues
.
"

This entry mechanism may also play a role
in disease progression.
Dr Côté said the findings could have implications for the development of serious diseases and some post-Covid-19 situations, such as the complex post-infection symptoms
known as "long Covid".

Reference: Identification and differential usage of a host metalloproteinase entry pathway by SARS-CoV-2 Delta and Omicron