Why is SARS-CoV2 so Infectious?

What are the structural features of the SARS-CoV-2 virus that allows it to attack human cells and spread so efficiently?

In an effort to understand the nature of this highly contagious virus, researchers have been drawing comparisons with SARS-CoV and this new coronavirus SARS-CoV2.

SARS-CoV and SARS-CoV-2 share 86% of the same genomic sequence. SARS-CoV was regarded as “the first pandemic of the 21st century” because it spread rapidly. But SARS-CoV-2 is spreading much quicker. In 2003, there was a reported 8,098 of SARS-CoV cases within 8 months with 774 deaths, which is a 10% case fatality ratio. By contrast, within 2 months of the start of the SARS-CoV2 outbreak, more than 82,000 people have been infected causing more than 2,800 deaths, which is a case fatality ratio of 3.4%

.

Much research has been done looking at what makes this new coronavirus more infectious.

Spike Proteins on the New Coronavirus

Spike proteins are what coronaviruses use to bind to the membrane of the human cells that they infect, and this binding process is activated by specific cellular enzymes. One such cellular receptor called angiotensin-converting enzyme 2 (ACE2) is what SARS-CoV2 uses to infect human cells. This same ACE2 receptor is what SARS-CoV in 2002 used for entrance into a cell.

But SARS-CoV-2 is different due to a specific structure that allows it to bind “at least 10 times more tightly than the corresponding spike protein of [SARS-CoV] to their common host cell receptor.”

This is partly due to the fact that the spike protein contains a site that recognizes and becomes activated by an enzyme called furin. The furin activation site “sets the virus up very differently in terms of its entry into cells, and possibly affects virus stability and hence transmission”, says Gary Whittaker, a virologist at Cornell University in Ithaca, New York.

In simple terms, Furins cleave precursor proteins and facilitates their conversion to a biologically active state. SARS CoV-2 can use furins to convert and activate their own proteins.

Furins are present in various human organs, such as the liver, the lungs, and the small intestines. The fact that this enzyme resides in all of these human tissues means that the virus can potentially attack several organs at once. But furins are expressed in significant concentration in the lungs.

It is the “furin-like cleavage site” recently discovered in SARS-CoV-2 spike proteins that may explain what makes SARS-CoV-2 transmit so efficiently and rapidly.

Knowing how the virus attaches to cells is important in understanding avenues for targeting and blocking SARS-CoV2 with treatments.