SARS-CoV-2 - How to Infect a Cell?

With the emergence of the COVID-19 global pandemic, scientists have been studying the mechanisms by which the virus SARS-Cov2 infects our cells in a chase to understand the disease’s symptoms and to find targets for new drug therapies.

Like other coronaviruses, SARS-Cov2 is a spherical enveloped virus composed of four structural proteins: spike, envelope, membrane and nucleocapsid. The viral genome is located inside it’s envelope and the spike protein irradiates all over the virus particle in a crown-like arrangement that names this group of viruses (coronavirus = virus with a crown in latin).

SARS-CoV-2 - How to Infect a Cell?

The use of the host cell’s machinery to produce new viral particles is a crucial step to viruses’ life cycle. To take control of the cell metabolism, SARS-Cov2 membrane has to be fused with the cell’s membrane in order to inject the viral genome into the cytoplasm. This fusion may occur in two ways, and the spike protein plays a key role on both of them.

The spike protein binds to the human angiotensin-converting enzyme 2 (ACE2), a protein found on many organs (e.g. lungs). The presence of an exclusive set of mutations seems to make this binding stronger than the one reported for SARS-Cov – the virus responsible for the 2003 SARS outbreak.

Another set of mutations also found in SARS-Cov2 let the TMPRSS2, an enzyme that is present on many human tissues, cut the spike protein in a way that prepares it to start the membrane fusion process.

SARS-CoV-2 - How to Infect a Cell?

Once the fusion process ends, the viral genome enters the cell and starts expressing the viral proteins: the cell has now become a slave.

SARS-CoV-2 - How to Infect a Cell?

Alternatively, the virus may enter the cell inside vesicles called endosomes. The spike protein is then activated by two enzymes (cathepsin B and L) commonly found inside these vesicles. This activation triggers the fusion process, this time with the endosomal membrane.

The aforementioned steps are promising therapeutic targets for new antiviral drugs, vaccines or antibodies that may help fight Covid-19.

SARS-CoV-2 - How to Infect a Cell?

See more: Nishiga et. al.