Publications by authors named "Thomas D Downes"
Article Synopsis
- * The article introduces a new method called top-down drug discovery (TD), which involves searching through a large database of fungi to find genetic locations that produce molecules targeting specific human proteins, like cyclin-dependent kinases (CDKs).
- * Researchers successfully discovered two new molecules that inhibit CDKs and improved one of them to enhance its selectivity and effectiveness, showcasing the potential of TD for developing innovative medicines.
COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 or MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two cysteine viral proteases essential for viral replication.
View Article and Find Full Text PDFFragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we describe a workflow for the design and synthesis of 56 3D disubstituted pyrrolidine and piperidine fragments that occupy under-represented areas of fragment space (as demonstrated by a principal moments of inertia (PMI) analysis).
View Article and Find Full Text PDF