SARS-CoV-2 virus hijacks protein machinery to enter cells and multiply

An international team of scientists have identified protein sequences that are hijacked by the SARS-CoV-2 virus to allow it to attach to cells, gain entry and multiply. This presents an opportunity to target these interactions with drugs that can either stop the virus from entering the cell or to prevent it from cloning itself inside the cell.

The findings of their research has been published in the journal, Science Signaling. One of the authors is Professor Denis Shields, UCD Professor of Clinical Bioinformatics and a Fellow at UCD Conway Institute. They did a computer analysis of the virus spike protein, and of the proteins on the host cell that bind it.

Professor Shields explains, “A protein can be imagined as a bundled-up necklace of beads, and small segments of beads on that necklace may have particular properties of use to the virus.

We looked for short segments (short, linear motifs called SLiMs) involved in binding the virus spike to proteins or receptors on the surface of our cells.

We also looked at the part of the receptors that anchor or stick inside the cell. Here, we found tiny regions that play key roles in helping the virus move further into the cell.”

SARS-CoV-2 virus hijacks the receptors and uses the short segments to their advantage; helping the virus attach, enter cell and replicate.

Vaccines against Covid-19 can offer protection against the disease. However, it is not yet known how long they will work for and whether, if too few people are vaccinated, it will reduce the overall protection.

We need to find drugs that can stop the SARS-CoV-2 virus from causing infection and illness. This research helps to better understand how the SARS-COV-2 virus enters our cells to infect us. It may be possible to develop targeted therapies that dampen viral infection and disease progression.

Professor Shields has recently been funded by Science Foundation Ireland to continue this research along with scientists in UCD and RCSI. Dr Virginie Gautier in UCD School of Medicine and Fellow, UCD Conway Institute is an expert in viruses while Dr Marc Devocelle in RCSI has expertise in the chemistry of short protein segments called peptides.

Together, they will use computer programmes to help design peptides that can mimic those the virus uses to get inside our cells. The researchers will then make these new peptides, analyse them in the laboratory and see how well they prevent SARS-CoV-2 from getting inside human cells and causing infection.

Professor Shields hopes that by rapidly designing reagents that can block the Covid-19 virus from entering human cells, they will identify potential new medicines that can be further tested against Covid-19 in humans.

"Our vision is that this project will contribute strongly to the arsenal of tools that scientists and doctors can use to tackle Covid-19 and other coronavirus illnesses."

Journal Citation
Mészáros et al., Sci. Signal. 14, eabd0334 (2021) 12 January 2021
Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications