Absolute quantification of SARS-CoV-2 proteins and their human targets for informing drug strategies and accelerating vaccine development

Lead Research Organisation: Imperial College London
Department Name: Life Sciences


Understanding how the SARS-CoV-2 virus is infectious and causes disease requires a deep understanding of how the infectious particle-the virus- assembles from its component parts, and can make copies of itself and then invade cells and humans. We plan to work out how its building blocks-its proteins in particular-are produced, in what form and how much of each is made. To do so, we will use a method that weighs a protein, and counts how many proteins are in a sample from cells infected with the virus. These numbers will inform strategies for vaccine development as well as offer a deeper understanding of how the virus forms.

We will use a method called Multiple-Reaction-Monitoring Mass Spectrometry (MRM-MS) with protein standards which we will manufacture in our laboratory. This methodology allows to directly measure absolute protein concentrations in complex biological samples. Our approach has great scope for upscaling, because any drug and vaccine development could adopt and benefit from our methodology.

We propose to produce bespoke labelled synthetic protein standards and measure the absolute SARS-CoV-2 proteome, including some post-translational modifications, of (i) the virion (likely 9 proteins); (ii) within infected human cell lines (about viral 29 proteins), (iii) including yet undetected proteins; (iv) alongside key human proteins (19 proteins) the virus interacts with and or are considered drug targets; (v) determine the antigen-antibody ratios following vaccination trials in mice and humans and (vi) provide said standards to other laboratories to enable them to conduct similar analytics.


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Title Quantitaive proteomics of viral proteins by reaction iion monitoring 
Description use of purified heavy isotope labelled protein standards in LC-Ms workflow to estimate viral protein amounts in a range of biological samples 
Type Of Material Biological samples 
Year Produced 2021 
Provided To Others? Yes  
Impact Method available from the PI and Co-I, will for a published pre print once data are finalised 
Description Masters student talk atimperial and mastesr students project (informatics ) at U Manchester, proteomics training workshop attenance by named Co_I Dr Schumacher. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact To offer PGRs and PGTs insights into Imperials activity in tackling the COVID crisis using proteomics
Year(s) Of Engagement Activity 2021