WEHI New Medicines & Diagnostics Special Seminar hosted by Dr Mahta Mansouri

Dr Ashley Taylor

Medicinal Chemist – Monash Institute of Pharmaceutical Sciences

Utilizing fragment-based drug design to develop a novel class of inhibitors for SARS-CoV-2 papain like protease 

L7W Seminar Room

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Including Q&A session

Please note this presentation will not be recorded

Over the last 2 decades there have been several viral outbreaks caused by members of the coronavirus family the largest being the COVID-19 pandemic of 2019-2022 which claimed over 7 million lives worldwide. With only 3 drugs currently approved by the FDA and the emergence of drug-resistant mutants, it is important to develop new therapeutics with novel mechanisms of action. This talk will cover a fragment-based screen of SARS-CoV-2 PLPro identifying a novel class of spiro chromanone inhibitors that bind adjacent to the active site. Subsequent fragment growing and merging strategies guided heavily by 30+ high resolution X-ray cocrystal structures have led to a greater than 10,000-fold increase in binding affinity with lead compounds displaying low nanomolar activity in biochemical and cellular antiviral assays. This presents an opportunity to develop a new class of anti-coronaviral medication suitable for current and future pandemics.

Dr Ashley Taylor is a medicinal chemist with expertise in both fragment-based drug discovery and structural biology. He obtained his PhD at Monash University under the supervision of Professor Martin Scanlon working on the development of small molecule inhibitors of Dengue RdRp. Ashley then completed a postdoc at Vanderbilt University (America) with Professor Stephen Fesik focusing on the development of PLPro inhibitors where he served as the lead chemist and crystallographer. This work has led to a patent and several publications. Ashley has recently returned to Monash University where he is focusing on broad spectrum flaviviral protease inhibitors.

All welcome!