G2P-UK; A National Virology Consortium to address phenotypic consequences of SARS-CoV-2 genomic variation

SARS-CoV-2 has caused 1.4 million deaths and has devastated economies worldwide. As SARS-CoV2 replicates and spreads, its RNA genome inevitably mutates. Mutations may confer altered properties of potential concern to human health, such as increased pathogenicity or transmissibility, or reduced sensitivity to prior immunity or antiviral drugs. Importantly, the imminent roll out of vaccination campaigns could provide strong selection pressure for escape from vaccine-induced immunity. We are a consortium ("G2P-UK") of UK virologists who will work openly with COG-UK and UK-CiC, to establish an experimental pipeline and shared resources (reagents, methodologies and model systems) to rapidly define the phenotypic impacts of SARS-CoV-2 mutations as they emerge. With three interconnected work packages we will obtain and distribute clinical isolates and engineered SARS-CoV-2 mutants (WP1), test the functional properties of the mutations in in vitro assays (WP2) and characterise their phenotype in culture and animal model systems (WP3). The choice of strains and mutations will be informed by a joint working group that includes COGUK members. Current virus strains will be immediately introduced into the pipeline, to accumulate a baseline of underpinning knowledge about SARS-CoV-2 behaviour, to validate the consortium working relationships and to seed mechanistic studies suitable for further research. Then, as variants of concern are detected, they will be prioritized for co-ordinated investigation in real time. By interpreting the biological consequences of SARS-CoV-2 mutations we will inform on the associated risks and vulnerabilities related to public health policy and clinical practice, including treatment strategies, diagnostics and infection control, and vaccination.