Synthesis of novel dual-inhibitors targeting SARS-CoV-2 Mpro

• Grant number: 20/07222-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2021
• End date: July 31, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Carlos Alberto Montanari
• Grantee: Felipe Cardoso Prado Martins
• Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated scholarship(s): 21/09433-3 - Synthesis of dual-inhibitors targeting SARS-CoV-2 Mpro and PLpro, BE.EP.DD

Abstract

The current outbreak of the COVID-19 and its subsequently classification of pandemic have led everyone's attention. Considering the fact that there is no treatment for SARS-CoV and MERS-CoV, it is urgent the development of a treatment that is able to act on the main protease of the SARS-CoV-2. This project focuses on the synthesis of novel inhibitors that acts on SARS-CoV-2 Mpro and also on secondary targets, such as CatL and/or CatB, making such molecules dual inhibitors. Considering the fact that our in-house compounds already known to inhibit CatL and CatB have a high degree of similarity among the compounds recently published as SARS-CoV-2 Mpro inhibitors, the idea is to modify these compounds in a way that the chemical backbone gets an even higher degree of similarity and, therefore, repurposing these compounds to also inhibit the coronavirus main protease. Chemical modifications through known synthetic reactions will be employed in order to achieve such goals. The compounds will be synthesized, purified and fully characterized and then tested through biochemical assays, performed by members of our group, in order to test each compounds affinity for the enzymes of interest. (AU)