Role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) papain-like protease protein (PLPro) in COVID-19 infection. SARS-CoV-2 infects cells using host ACE2 and TMPRSS2 receptors. After infection, the virus uses the host transcription machinery and transcribes its early gene containing Non-structural protein (Nsp)1, Nsp2, Nsp3 and Nsp4 as a proprotein. PLPro, a papain like protease (PLP), is autocleaved from Nsp3 protein due to its intrinsic proteolytic function. SARS-CoV-2 PLPro then cleaves Nsp1–Nsp2, Nsp2–Nsp3 and Nsp3-Nsp4 junctions of the proprotein to give rise to the individual proteins. PLPro acts like a deubiquitinase and deISGylation enzyme on endogenous host proteins to abrogate host specific innate immune response.