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Department of Biochemistry

A scientist working in the laboratory.

Executive summary

As the spread of COVID-19 continues to wreak devastating effects around the world, researchers across the University of Cambridge are bringing their skills to bear on key projects aimed at combating the virus. As a University, we are working in close collaboration with clinical and industry partners, academic colleagues and public bodies in the UK and around the world to ensure our work makes a substantive contribution at this moment of acute need.

There are currently no therapies and no vaccine effective against COVID-19. Control measures are limited to surveillance, isolation and quarantine of infected patients, and limiting human population movement into and from infected areas. There is an urgent need for therapeutic interventions, and an understanding of disease mechanisms is fundamental to developing such therapies.

As such, a critical part of our work at Cambridge involves focusing our world-leading expertise in the fundamental life sciences on understanding the mechanisms by which SARS-CoV-2, the virus that causes COVID-19, replicates, infects its hosts, triggers immune responses, and is transmitted onwards. The findings of this research will ensure that diagnostics, treatments and mitigation strategies developed to combat COVID-19, can be as targeted, accurate and effective as possible. Understanding how this lethal disease operates is key to halting its spread.

Professor Luca Pellegrini, Professor of Structural Biology in our Department, leads a Research Group working to determine the molecular mechanisms of genomic stability. As the COVID-19 pandemic has spread across the world, the team's work has pivoted to focus on the molecular basis for the acute inflammatory response to SARS-CoV-2. Their work will play a crucial role in understanding how the human immune system responds to infection by SARS-CoV-2, why some people become seriously ill and some do not, and which measures might be effective in mitigating against this. This research will pave the way for targeted therapeutic interventions, and will add another weapon to the scientific community's arsenal in the fight against COVID-19.

We are seeking committed philanthropic partners to support Professor Pellegrini's work, and in doing so to work with us to contribute to understanding and combating this lethal virus.


The challenge

The SARS-CoV-2 virus is causing widespread, mass-scale disease because, in some patients, it evokes a strong inflammatory response that impairs lung function. However, the molecular mechanisms the virus uses to do this are not yet understood. Understanding these mechanisms would enable the design and implementation of anti-viral therapeutics, inform treatment strategies, and also help to predict whether patients are likely to become seriously ill.

The work of Professor Pellegrini and his team focuses on the protein-protein interactions (PPI) between the SARS-CoV-2 virus and the human proteome. A comprehensive map of these interactions was released at the end of March 2020 by an international consortium of researchers led by the Krogan Laboratory at the Quantitative BioSciences Institute in San Francisco.

Professor Pellegrini and his team analysed this data, and found evidence to suggest that the viral protein Nsp1 interferes with the activity of human DNA Polymerase alpha (Pol alpha)/primase, a long-standing focus of research in his lab. Interestingly, in addition to its well-established role in DNA replication, Pol alpha has a newly discovered function in controlling the type I interferon response of the immune system. By suppressing Pol alpha's activity, Nsp1 would drive the inflammatory response that leads to the acute respiratory crisis suffered by some patients with the virus. The team are now working to understand the molecular and structural basis for how this occurs. The data from this work will yield important insights into the molecular mechanisms deployed by the virus to cause SARS, and a structural rationale for the design of small-molecule inhibitors of Nsp1 function, which could then be utilised as anti-viral therapeutics.


Supporting our work

A philanthropic gift of £46,000 would support the first six months of this critical research project. Specifically, these funds would provide:

  • The salary for a Senior Research Associate to work on the project,
  • Research materials, including consumables to undertake the proposed experiments,
  • Access charges for Biophysics and Cryo-EM facilities.

This work has the potential for enormous impact on our understanding of the mechanisms of SARS-CoV-2, and on the development of effective and targeted therapeutics. We are hugely grateful for your interest in supporting COVID-19-related research at Cambridge, and would be delighted to discuss any aspect of this opportunity in more detail, should you wish.


For further information, or to find out more about our work, please contact:

Linda Hindmarsh

Senior Associate Director – Biological Sciences
Cambridge University Development and Alumni Relations

Contact details

Research Facilitator  Paula Bibby (Research Facilitator)

Telephone  +44 (0)1223 339321