Molecular design and synthesis of coronavirus SARS-CoV-2 main protease (SARS CoV-2 Mpro) inhibitors

• Grant number: 20/04653-2
• Support Opportunities: Regular Research Grants
• Duration: May 01, 2020 - April 30, 2022
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Carlos Alberto Montanari
• Grantee: Carlos Alberto Montanari
• Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/18009-4 - Molecular design, synthesis and trypanocidal activity of cruzain reversible covalent inhibitors, AP.TEM
• Associated scholarship(s): 20/06543-0 - Molecular design and synthesis of Coronavirus SARS-CoV-2 main protease (SARS Cov-2 Mpro) inhibitors, BP.PD

Abstract

The current worldwide outbreak of the coronavirus with a pandemic declared by the World Health Organization (WHO) is beginning to strike in Brazilian lands. This pandemic urged us to start an emergency project in the search for new proteases inhibitors of the main coronavirus protease (SARS Cov-2 Mpro) as antiviral agents acting on the coronavirus. Several cysteine protease inhibitors (CPs) under development in our group have 60-70% similarity in the coronavirus SARS 3C protease (CHEMBL3927), directly in the SARS coronavirus (CHEMBL612575) and also in feline coronavirus (CHEMBL612744). Mostly, our inhibitors are similar to the new SARS Cov-2 Mpro inhibitors. Thus, we will initially test the entire NEQUIMED/IQSC/USP database in phenotypic tests that will be carried out at the Institute of Biomedical Sciences, ICB/USP. Concomitantly, we will modify the structures of our CP inhibitors to improve the percentage of similarity to the best known inhibitors and for which we will seek evidence of action on the disseminated coronavirus in Brazil. In addition, we will immediately employ our artificial intelligence tools with machine learning to select test candidates from the drugs currently in therapy, experimental and investigational drugs and those drug candidates that are in clinical phases. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BONATTO, VINICIUS; SHAMIM, ANWAR; ROCHO, FERNANDA DOS R.; LEITAO, ANDREI; LUQUE, F. JAVIER; LAMEIRA, JERONIMO; MONTANARI, CARLOS A.. Predicting the Relative Binding Affinity for Reversible Covalent Inhibitors by Free Energy Perturbation Calculations. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 61, n. 9, p. 4733-4744, SEP 27 2021. (20/04653-2, 20/06543-0, 18/15904-6)