View all news

Neuropilin-1 drives SARS-CoV-2 infectivity, finds breakthrough study

Neuropilin-1 (NRP1) is a host factor for SARS-CoV-2 infection. The image shows human cells infected with SARS-CoV-2 and expressing viral proteins (shown in green). Removal of NRP1 from cells or treating cells with a drug or an antibody targeting NRP1 reduces SARS-CoV-2 infection University of Bristol

20 October 2020

In a major breakthrough, an international team of scientists led by the University of Bristol has potentially identified what makes SARS-CoV-2 highly infectious and able to spread rapidly in human cells. The findings, published in Science today [20 October] describe how the virus’s ability to infect human cells can be reduced by inhibitors that block a newly discovered interaction between virus and host, demonstrating a potential anti-viral treatment.

Unlike other coronavirus, which cause common colds and mild respiratory symptoms, SARS-CoV-2, the causative agent of COVID-19, is highly infective and transmissive. Until now, major questions have remained unanswered as to why SARS-CoV-2 readily infects organs outside of the respiratory system, such as the brain and heart.

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 by which the ‘Spike’ protein recognises human cells is central to the development of antiviral therapies and vaccines to treat COVID-19.

In this breakthrough study, the research groups in Bristol’s Faculty of Life SciencesProfessor Peter Cullen from the School of BiochemistryDr 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, used multiple approaches to discover that SARS-CoV-2 recognises a protein called neuropilin-1 on the surface of human cells to facilitate viral infection.

Yohei, Boris and Pete explained: "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. This led us to propose a simple hypothesis: could the Spike protein of SARS-CoV-2 associate with neuropilin-1 to aid viral infection of human cells? Excitingly, in applying a range of structural and biochemical approaches we have been able to establish that the Spike protein of SARS-CoV-2 does indeed bind to neuropilin-1.

"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. Importantly, by using monoclonal antibodies - lab-created proteins that resemble naturally occurring antibodies - or a selective drug that blocks the interaction we have been able to reduce SARS-CoV-2’s ability to infect human cells. This serves to highlight the potential therapeutic value of our discovery in the fight against COVID-19."

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 anti-viral 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.”

The SARS-CoV-2 work at Bristol was facilitated by Dr Andrew Davidson and Dr David Matthews, Readers in Virology in the School of Cellular and Molecular Medicine and Bristol UNCOVER and through key collaborations with Professor Brett Collins of the University of Queensland, Brisbane, Australia, and Professor Tambet Teesalu of University of Tartu, Estonia.

The study was funded by grants from the European Research CouncilMRCWellcome TrustLister Institute of Preventive MedicineElizabeth Blackwell Institute, and Swiss National Science Foundation.

Paper

'Neuropilin-1 is a host factor for SARS-CoV-2 infection' by Daly, Simonetti, Klein et al in Science

Further information

About coronavirus (SARS-CoV-2)
The surface of the coronavirus particle has proteins sticking out of it known as Spike proteins which are embedded in a membrane.  They have the appearance of tiny little crowns, giving the virus its name (corona). Inside the membrane is the viral genome wrapped up in other proteins. The genome contains all the genetic instruction to mass produce the virus. Once the virus attaches to the outside of a human cell, its membrane fuses with the human cell membrane and its genetic information into the human cell.  Next, the virus instructs the cell to start replicating its genome and produce its proteins. These are then assembled into many new copies of the virus which, upon release, can infect many more cells. The viral proteins play diverse further roles in coronavirus pathology.

Support our COVID-19 research
Bristol’s researchers are part of a global network of scientists responding urgently to the challenge of the coronavirus pandemic.

Find out how you can support their critical work

Bristol UNCOVER Group
In response to the COVID-19 crisis, researchers at the University of Bristol formed the Bristol COVID Emergency Research Group (UNCOVER) to pool resources, capacities and research efforts to combat this infection.

Bristol UNCOVER includes clinicians, immunologists, virologists, synthetic biologists, aerosol scientists, epidemiologists and mathematical modellers and has links to behavioural and social scientists, ethicists and lawyers.

Follow Bristol UNCOVER on Twitter at: twitter.com/BristolUncover

For more information about the University of Bristol’s coronavirus (COVID-19) research priorities visit: http://www.bristol.ac.uk/research/impact/coronavirus/research-priorities/

Bristol UNCOVER is supported by the Elizabeth Blackwell Institute
Find out more about the Institute’s COVID-19 research looking into five key areas: virus natural history, therapeutics and diagnostics research; epidemiology; clinical management; vaccines; and ethics and social science.

Edit this page