The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel type of coronavirus first reported in 2012. MERS-CoV has a higher case/fatality rate (30%) than severe acute respiratory syndrome coronavirus (SARS-CoV) (10%). Coronaviruses cause mild to moderate upper-respiratory tract illnesses, and the most deadly infections are from MERS-CoV and SARS-CoV. They encode multifunctional enzymes, known as papain-like proteases (PLpro), that process the viral replicase polyprotein, deubiquitinate (DUB), and deISGylate host cell proteins. There are currently no vaccines or therapeutics that could treat or prevent coronavirus infections. In this study, a promising MERS PLpro inhibitor was discovered that could lead to the development of an effective anti-MERS-CoV drug. A primary high-throughput screen of 25,000 compounds was performed to identify MERS-CoV PLpro inhibitors, and a subset of inhibitors was selected for further experimentation. A single compound (MRL-05-2014) that inhibits MERS-CoV PLpro with an IC<sub>50</sub> value of 20.6 ± 1.0 µM was identified. Future studies will be aimed at improving the inhibitory potency of MRL-05-2014.

Discovery of a potential Middle East respiratory syndrome (MERS) PLpro inhibitor for the development of anti-MERS-CoV drugs

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.