In early 2020, the outbreak of SARS-CoV-2 caused laboratories to close and scientists to work from home. With a view to tackling the virus, we joined forces with labs across Europe to contribute to the growing research on SARS-CoV-2. We focused on SARS-CoV-2 papain-like protease, PLpro, and compared it to previously characterised PLpro from SARS. PLpro can cleave small proteins such as ubiquitin or ISG15 from target proteins. We found that SARS-CoV-2 PLpro specifically cleaves ISG15 from its substrates, compared to SARS PLpro that specifically cleaves ubiquitin.

Here we present a new regulatory mechanism of autophagy, which influences the conjugation and de-conjugation of autophagy modifiers to autophagosomes. TBK1 phosphorylates LC3C and GABARAP-L2, which impedes LC3 binding to the processing enzyme ATG4.

https://doi.org/10.15252/embr.201948317