The first Emmott lab paper “Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential” is now published in peer-reviewed form, having previously been available as a preprint on bioRxiv.
In this work we studied protease activity during SARS-CoV-2 infection. We identified multiple novel cleavage sites in viral proteins including the key S and N antigens. We also found cellular proteins cleaved by the viral Mpro and PLP proteases. In contrast to the prevailing model that proteolytic cleavage is primarily to inhibit cellular activities detrimental to infection, we found that these cellular proteins were essential for efficient virus replication, and that siRNA or inhibitor treatment targeting this proteins could reduce SARS-CoV-2 RNA levels and levels of infectious virus produced in cell culture models.