University of Glasgow: NATIONAL CONSORTIUM TO STUDY THE THREATS OF NEW SARS-COV-2 VARIANTS

The ‘G2P-UK’ National Virology Consortium* 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 will bring together leading virologists from 10 research institutions, including the MRC-University of Glasgow Centre for Virus Research (CVR). They will work alongside the COVID-19 Genomics UK (COG-UK) consortium, which plays a world-leading role in virus genome sequencing, and Public Health England to boost the UK’s capacity to study newly identified virus variants and rapidly inform government policy.

Professor Massimo Palmarini, co-lead and Director of the CVR, said: “Understanding the unique properties of a single SARS-CoV-2 variant requires experiments that can last several weeks. Hence, it is absolutely essential to carry out studies on SARS-CoV-2 variants as a coordinated effort at the UK level.”

The CVR, along with others in the consortium, will focus on different areas but primarily on synthesising by “reverse genetics” viruses with mutations of interest for downstream studies. They scientists will use molecular biology ‘tricks’ to synthesise viruses with the mutations the scientists are interested in studying further.

In addition, the CVR will develop, in collaboration with colleagues in COG-UK, an online tool that allows the easy search of specific mutations in a vast number of viral sequences that the UK has generated.

The consortium is led by Professor Wendy Barclay, from Imperial College London, who 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.”

Science Minister Amanda Solloway said: “The UK has a world class genomics capability, and it is thanks to the work of our leading medical scientists and researchers that our scientists have been able to identify new variants of coronavirus at speed.

“This crucial new research project will help us to understand not only the extent to which these new variants spread and their risks, but also how resistant they are to vaccines and treatments, so that we can tailor our response to help defeat this virus once and for all.”

Professor Dame Ottoline Leyser, Chief Executive, UK Research and Innovation, which funded the study, said: “One of the real strengths of the UK’s scientific response to the pandemic has been the way that researchers from all over the country have pooled their expertise to deliver big results, fast. This new national consortium will study the effects of emerging variants on transmission, disease severity, and vaccine effectiveness – building on the work of the COVID-19 Genomics UK Consortium, which has been so effective in identifying new variants.

“This is critical research which will feed into government decision-making on a daily basis.”

Mutations in the virus’s genome occur naturally and some of these will be inconsequential, while others will change how it functions.

As new virus variants arise, the consortium will flag the riskiest variants, such as those associated with fast spreading virus clusters, to study. They will also create standardised versions of the virus with and without each mutation, so they can study the effects of each change individually.

Other teams in the consortium will then 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.

The researchers will then use cell cultures and animal models to study if the virus mutations alter the immune response, virus transmissibility, the severity of the disease it causes, or the effectiveness of vaccines and treatments.

The researchers 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.

Professor Bryan Charleston, co-lead from BBSRC-sponsored The Pirbright Institute, said: “We need to understand quickly whether new variants spread faster, cause more severe disease, escape immunity or infect other animals more readily.”

Professor Michael Malim, co-lead from King’s College London, said: “It’s really important for the strengths and breadth of UK virology to come together and develop an evidence-base to explain the biological impacts of viral variants, such as possible resistance to vaccine induced immunity, and inform how we should respond and plan for the future.”

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.