Development of small molecule inhibitors of the SARS-CoV-2 protease PLpro for the treatment and prevention of Covid-19

The SARS-CoV-2 pandemic is a global health emergency that highlighted the need for new antiviral medicines and better pandemic preparedness. Our drug-discovery program focusses on a critical protein present in all coronaviruses, the papain-like protease PLpro. PLpro is essential for viral replication, but also stops our alarm systems to respond to viral infection, To achieve the latter, it removes 'ubiquitin' and ubiquitin-like signals required for inflammation and anti-viral signalling. Our world-leading experts in ubiquitin research, drug-discovery and infectious disease biology have leveraged our state-of-the-art facilities to identify new drug candidates to block PLpro. We have screened > 400,000 small molecule compounds and identified new chemical scaffolds that inhibit PLpro from SARS-CoV-2 without affecting human enzymes. Our program will deliver new antivirals to prevent or treat COVID-19 and also develop a library of efficacious drug candidates to combat future coronavirus outbreaks