Neuropilin-1 plays key in driving SARS-CoV-2 infectivity: Study

October 22, 2020 0 By FM

In a major breakthrough study, researchers from the University of Bristol has unveiled that unlike other coronaviruses the SARS-CoV-2 virus attacks by recognising a protein called neuropilin-1 on the surface of human cells that make it highly infectious. The findings may answer as to why SARS-CoV-2 readily infects organs outside of the respiratory system, such as the brain and heart, the researchers say.

The study also describes how the virus’s ability to infect human cells can be reduced by inhibitors that block the newly discovered interaction between virus and host, demonstrating a potential antiviral treatment.

Unlike other coronaviruses, which causes common colds and mild respiratory symptoms, SARS-CoV-2, the causative agent of COVID-19, is highly infective and transmissive. To infect humans, SARS-CoV-2 must first attach to the surface of human cells that line the respiratory or intestinal tracts. Once attached, the virus invades the cell then replicates multiple copies of itself. The replicated viruses are then released leading to the transmission of SARS-CoV-2.

The virus’s process of attachment to and invasion of human cells is performed by a viral protein, called the ‘spike’ protein. Understanding the process which the ‘spike’ protein recognises human cells is central to the development of antiviral therapies and vaccines to treat COVID-19.

“In looking at the sequence of the SARS-CoV-2 spike protein we were struck by the presence of a small sequence of amino acids that appeared to mimic a protein sequence found in human proteins which interact with neuropilin-1,” explained Professor Peter Cullen from the School of Biochemistry, Dr Yohei Yamauchi, Associate Professor and virologist from the School of Cellular and Molecular Medicine, and Dr Boris Simonetti, a senior researcher in the Cullen lab in Bristol’s Faculty of Life Sciences.

In applying a range of structural and biochemical approaches, the researchers have been able to establish that the spike protein of SARS-CoV-2 does indeed bind to neuropilin-1 to aid viral infection of human cells.

“Once we had established that the Spike protein bound to neuropilin-1 we were able to show that the interaction serves to enhance SARS-CoV-2 invasion of human cells grown in cell culture,” they said.

The researchers highlighted that by utilising the monoclonal antibodies or a selective drug that blocks the interaction they have been able to reduce SARS-CoV-2 virus’s ability to infect human cells. 

Intriguingly, scientists at the Technical University of Munich, Germany and the University of Helsinki, Finland, have independently found that neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity.

Together the Bristol researchers concluded: “To defeat COVID-19 we will be relying on an effective vaccine and an arsenal of antiviral therapeutics. Our discovery of the binding of the SARS-CoV-2 spike to neuropilin-1 and its importance for viral infectivity provides a previously unrecognised avenue for anti-viral therapies to curb the current COVID-19 pandemic.”