Dr Simone Di Micco’s group from the European Biomedical Research Institute of Salerno specialises in the design of bioactive compounds. At the onset of the COVID-19 pandemic, they naturally started to focus on SARS-CoV-2 and ways to design active molecules against the virus. They quickly identified zonulin inhibitor AT1001 as a promising anti-SARS-CoV-2 candidate through its binding to the catalytic domain of SARS-CoV-2 main protease Mpro, which is essential for the virus life cycle. In need of specific structural biology expertise to understand the mechanism of action of AT001, Dr Di Micco received, through ISIDORe, free of charge access to the automated X ray crystallography pipeline of INSTRUCT-ERIC Node EMBL Grenoble. The studies performed there revealed exactly how AT1001 binds to Mpro and informed Dr Di Micco as to how the drug design process should be refined for generating improved second‑generation peptides.This resulted in the characterization of a compound with both promising anti-SARS-CoV-2 activity and very low cellular toxicity.
