SYNTHESIS, CHARACTERIZATION AND ANTIVIRAL STUDIES OF NOVEL Pd(II) COMPLEXES WITH AMINOADAMANTANES

• Grant number: 23/14245-7
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: December 10, 2023
• End date: March 08, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Pedro Paulo Corbi
• Grantee: Laura Barros Silva
• Supervisor: Raphael Enoque Ferraz de Paiva
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Donostia International Physics Center, Spain
• Associated to the scholarship: 22/08320-3 - Synthesis, characterization and antiviral activity studies of Pd(II) with aminoadamantanes complexes, BP.IC

Abstract

Aminoadamantanes, such as amantadine, memantine and rimantadine, are molecules obtained from the functionalization of adamantane that present pharmacological activities. Amantadine and rimantadine are used as agents in the prevention and treatment of Influenza A virus infections, while memantine is used in medicine to treat neurodegenerative conditions such as Alzheimer's disease. Recent studies point to these molecules as potential agents to new viral infections. Recent publications from our group showed that coordination of these aminoadamantanes with platinum can enhance their pharmacological activities. Palladium has an electronic structure and coordination modes similar to platinum, in addition to having known antineoplastic and antimicrobial activities, which motivates the use of this metal in this work. Infectious diseases caused by viruses represent a threat to global health, especially those for which there is no known specific medication for their treatment. We have recently been faced with a major health issue caused by the Covid-19 pandemic, which made the need for new strategies to develop medicines with antiviral activities, especially with action against the SARS-COV-2 virus. With this in mind, palladium complexes with amantadine, memantine and rimantadine were synthesized and characterized in the last year in our group. This research has received funds from FAPESP (São Paulo State Research Council, Brazil). The antiviral activity of the palladium(II) complexes was tested against arboviruses and also SARS-COV-2, and the complexes were significantly more active than their precursors in inhibiting viral replication. In order to investigate the mechanisms of action of these compounds, this project proposes the conduction of specific biophysical assays to evaluate the interaction between the complexes and SARS-COV-2 proteins in combination with theoretical (molecular docking) studies. The main purpose of the project is to evaluate the interaction between the Pd(II) complexes and SARS-COV-2 proteins in order to understand the mechanisms behind their antiviral properties. Specifically, we aim to evaluate the action of the Pd-atd, Pd-mtn and Pd-rtd complexes in inhibiting the viral helicase or the interaction between the Spike protein and the ACE2 receptor. Furthermore, once a hit compound is identified via plate-based assay, the project aims to use mass spectrometric techniques to identify the binding site between the compound and the protein. These experiments shall be carried at Donostia International Physics Center, San Sebastián, Spain, under the supervision of Dr. Raphael Enoque Ferraz de Paiva.