Synthesis of dual-Inhibitors Targeting SARS-CoV-2 Mpro and PLpro

Abstract

The pandemic of COVID-19 has drawn everyone's attention. Unfortunately, since the appearanceof the SARS and MERS viral infections in the 2000s, no treatments have been developed thusfar. Therefore, it is urgent the production of a molecule to serve as a treatment that can actagainst SARS-CoV-2, the causative agent of COVID-19. This project aims at synthesizing novelinhibitors that can potentially work against SARS-CoV-2 Mpro and/or PLpro, ideally as dual inhibitors. Considering our group far-reaching expertise in developing and synthesizing humancathepsins and parasitic protease inhibitors, and considering also the high degree of similaritybetween human, parasitic and viral proteases, we are interested in the synthesis of new compoundsinspired by the real possibility of designing new inhibitors with dual action on the proposedtargets. To achieve this, we will incorporate the immeasurable expertise of Prof. Stockwell whohas recently developed an excellent drug candidate with high potency over SARS-CoV-2.Therefore, different scaffold modifications will be carried out in order to achieve a better jointaffinity towards Mpro and PLpro. Chemical modifications through known synthetic reactions willbe employed in order to achieve such goals. The compounds will be synthesized, purified, fullycharacterized, and then tested through biochemical assays, performed by members of our group,in order to test each compound's affinity for the enzymes of interest.