Optimizing polar, small inhibitors of a viral cysteine protease to identify a lead for an oral COVID‑19 treatment
The COVID‑19 pandemic has caused incredible social, personal and economic upheaval and as of early May 2020 killed 275 000 people world-wide and, tragically, is projected to kill millions more. COVID‑19 is caused by the SARS-CoV2 (SARS2) virus, which is a coronavirus closely related to SARS. These viruses infect cells and using the host’s enzymes and virally encoded proteins create copies of themselves. These viral proteins are different than the host ones and are key targets to stop the viral replication. One such protein for SARS2, nicknamed 3CLP, is key to liberating the viral proteins in order to enable viral replication. Last month compounds we tested strongly inhibited the SARS2 3CLP and were able to inhibit SARS2 replication in a cell-based assay. This proposal is to design and make modifications of those compounds to better inhibit SARS2 and also optimize drug-like properties to discover a Lead compound for the ultimate development of an oral drug to treat COVID-19.