Planning and synthesis of boronic derivatives acylhydrazones as main protease inhibitors (3CLpro) of SARS-CoV-2

• Grant number: 22/04709-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2022
• End date: August 31, 2023
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Chung Man Chin
• Grantee: Diogo Boreski
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Sars-CoV-2 is a virus from Coronaviridae family first identified in 2019. This ²-coronavirus, whose caused COVID-19 disease was responsible for the recent state of emergency in the world. Infecting more than 345,000,000 people worldwide, COVID-19 was also responsible for the deaths of more than 5,000,000 people. To date, there are no effective treatments against COVID-19, so the need for new antiviral drugs that are specific and selective for SARS-CoV-2 and its development in the organism is required. The SARS-CoV-2 life cycle is characterized by the presence of specific proteins responsible for ensuring its replication. The Mpro enzyme (Main protease), also called 3CLpro (3 Chymotrypsin-like protease) is an essential protease for SARS-CoV-2 survival, which cleaves polyproteins into smaller coding sequences that encode other viral proteins that are also important for the virus life cycle. Thus, proteases become a specific target and one of most relevant interest for the search for inhibitors. Based on boronic acids and hydrazone derivatives, thus are promising and important compounds in medicinal chemistry, this project proposes the synthesis of composts, which based on molecular alterations through computational methods (molecular docking), aim to inhibit the viral protease Mpro. The discovery and investigation of new compounds are fundamental for the elucidation of interactions of the molecule with its target, optimizing the understanding of specific inhibitors and the comprehension of key chemical groups for the COVID-19 treatment.