Pirbright is to take a lead role in a new national research project to study the effects of emerging mutations in SARS-CoV-2. The ‘G2P-UK’ National Virology Consortium with £2.5 million of funding from UK Research and Innovation (UKRI) will study how mutations in the virus affect key outcomes such as how transmissible it is, the severity of COVID-19 it causes, and the effectiveness of vaccines and treatments.
The Consortium brings together leading virologists from 10 research institutions including The Pirbright Institute and they will work alongside Public Health England (PHE) and the COVID-19 Genomics UK (COG-UK) consortium, which plays a world-leading role in virus genome sequencing, to boost the UK’s capacity to study newly identified virus variants and rapidly inform government policy.
Mutations in the SARS-CoV-2 genome occur naturally and many of these will be inconsequential; however, a small number will change how the virus functions. As new virus variants arise, the consortium will flag the riskiest variants requiring research, such as those associated with fast spreading virus clusters. They will also create standardised versions of the virus with and without each mutation, so they can study the effects of each change individually. Pirbright’s role is to focus on research around mutations in the spike protein, how these changes can influence the virus’s ability to enter cells and how these genetic alterations might affect its ability to spread and cause disease. Professor Bryan Charleston, Pirbright’s Director who leads a work package, commented: “We need to understand quickly whether new variants spread faster, cause more severe disease, escape immunity or infect other animals more readily.”
Teams in the consortium will study how these new variants alter the virus proteins, particularly the key spike protein on the surface. This is important because changes to the spike protein can affect transmissibility and could potentially alter the effectiveness of vaccines and antibodies that target the protein.
Dr Dalan Bailey, head of the Viral Glycoproteins Group at Pirbright added: “We will be examining whether naturally acquired mutations in the SARS-CoV-2 Spike protein change any of the fundamental properties of this virus, for example how well it replicates. This is in order to better understand the risk of novel variants and to learn more about the biology of this virus.”
Professor Wendy Barclay, from Imperial College London, who is leading the consortium said: “The UK has been fantastic in sequencing viral genomes and identifying new variants – now we have to better understand which mutations affect the virus in a way that might affect our control strategies. We are already working to determine the effects of the recent virus variants identified in the UK and South Africa and what that means for the transmission of SARS-CoV-2 and vaccine effectiveness.
“Now the virus has circulated in humans for more than one year and is prevalent all around the world, we’re in a phase where the virus is constantly throwing up new variants and we need to gear up to assess the risk they pose, and to understand the mechanisms by which they act.”
Researchers across the consortium will study how readily the virus variants transmit by direct contact or airborne routes in animal models. They will also study the impact on disease severity, such as lung damage and breathing impairment, which correlate with symptoms typical of human COVID-19.
Additionally, they will determine whether mutations in the spike protein enable the virus to escape the immune response generated by either the vaccine or immune memory from earlier infection.
By setting up a streamlined, coordinated and openly communicated programme, that operates across the UK to study the latest virus mutations simultaneously in several labs with complimentary experimental methods, the researchers aim to produce faster, reliable results to feed into public health policy and clinical practice.
The consortium has been named ‘G2P-UK’, standing for ‘genotype to phenotype’. They will study how changes in the virus genes (the ‘genotype’) alters the ‘phenotype’. The term ‘phenotype’ describes the observable characteristics of an organism.
The scientists are based at ten research institutions: Imperial College London, The Pirbright Institute, King’s College London, University of Glasgow, University of Bristol, University of Liverpool, UCL, University of Oxford, University of Cambridge and the Francis Crick Institute.
