SARS-CoV-2 encodes two proteases, the papain-like protease (PLpro) and main protease (3LCpro). PLpro cleaves nsp1, nsp2 and nsp3. 3LCpro cleaves the remaining 13 non-structural proteins. PLpro also removes ubiquitin-like ISG15 protein modification as well as Lys48-linked polyubiquitin, both of which are essential for the inducion of cellular interferon responses. Therefore, inhibitory compounds against the PLpro activity is a valiable strategy to combat this viral infection.
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