A protease activity profiling strategy to inhibit cell-to-cell transmission of SARS-CoV-2

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SARS-CoV-2 is a new coronavirus, which emerged in late 2019, has infected tens of thousands in China, and has now spread into 40 countries. To break the chain of transmission, host and viral determinants that increase the transmissability of SARS-CoV-2 need to be identified, in order to develope suitable and effective intervnetions. Two main determinants of virus transmission are the host cellular proteases that cleave the viral Spike protein to make it more infectious, and the viral Spiek itself that has evolved to carry additional protease-cleavage sites, allowing host expansion. We aim to identify these cellular proteases and inhibit them to block virus transmission. We also aim to generate virus with Spike proteins that cannot be cleaved, to determine whether we can arrest their spread. Collectively these approaches will be used to inform production of therapeutic molecules (against the proteases) and design of vaccines (against the viral Spike).