Characterization and Noncovalent Inhibition of the Deubiquitinase and deISGylase Activity of SARS-CoV‑2 Papain-Like Protease

• Published in: ACS infectious diseases Vol. 6; no. 8; pp. 2099 - 2109
• Main Authors: Freitas, Brendan T, Durie, Ian A, Murray, Jackelyn, Longo, Jaron E, Miller, Holden C, Crich, David, Hogan, Robert Jeff, Tripp, Ralph A, Pegan, Scott D
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 14.08.2020
• Subjects: Amino Acid Sequence; Animals; Betacoronavirus - enzymology; Binding Sites; Chlorocebus aethiops; Coronavirus 3C Proteases; Coronavirus Infections - virology; COVID-19; Cysteine Endopeptidases - chemistry; Cysteine Endopeptidases - metabolism; Cytokines - antagonists & inhibitors; Cytokines - chemistry; Cytokines - metabolism; Deubiquitinating Enzymes - antagonists & inhibitors; Humans; Naphthalenes - pharmacology; Pandemics; Pneumonia, Viral - virology; Protein Binding; Protein Conformation; SARS-CoV-2; Substrate Specificity; Ubiquitin - metabolism; Ubiquitins - antagonists & inhibitors; Ubiquitins - chemistry; Ubiquitins - metabolism; Vero Cells; Viral Nonstructural Proteins - antagonists & inhibitors; Viral Nonstructural Proteins - chemistry; Viral Nonstructural Proteins - metabolism; Virus Replication - drug effects; COVID-19; severe acute respiratory syndrome 2; coronavirus; PLpro; ISG5; ubiquitin

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, is a novel human betacoronavirus that is rapidly spreading worldwide. The outbreak currently includes over 3.7 million cases and 260,000 fatalities. As a betacoronavirus, SARS-CoV-2 encodes for a papain-l...