University of Cagliari
PhD Program in Life, Environmental and Drug Sciences
- Role
- Dottorando
- salvatore.nieddu@unica.it
- Address
- Cittadella Universitaria di Monserrato, S.S. 554 bivio per Sestu | 09042 Monserrato CA
Curriculum: Biomedical
Supervisor: Francesca Esposito
Co-Supervisor: Angela Corona
Curriculum Vitae
Salvatore graduated with honor in Biology in July 2021 at the University of Sassari discussing a bachelor thesis titled “Increase in RAB10 phosphorylation in transgenic Drosophila lines expressing human LRRK2”, under the supervision of Professor Ciro Iaccarino.
He graduated with honor in a Master’s degree in Molecular and Cellular Biology in July 2023. His thesis, titled “Identification of novel inhibitors of unwinding and ATPase activities of nsp13 of SARS-CoV-2”, focused on the screening of small molecules targeting the helicase activity of SARS-CoV-2. This research was conducted in the virology laboratory of Professor Enzo Tramontano at the University of Cagliari, under the supervision of Professor Angela Corona. Thanks to the Erasmus+ Traineeship Programme, before graduation he spent 3 months in the virology laboratory of Ben Berkhout at the AMS of Amsterdam where he focused on the study of the uORF in the 5’ UTR of HCoVs and the role that they can play on the translation of the main ORF.
Since October 2023, Salvatore has been a PhD student in the XXXIX Cycle of the PhD Program in Life, Environment and Drug Sciences at the University of Cagliari. Under the supervision of Professor Francesca Esposito, his current research focuses on the identification of novel inhibitors targeting the proteases of flaviviruses. His research activity is supported by periodic scholarship financed by PNRR Extentended Paternship INFACT: One Health Basic and Translational Actions Addressing Unmet Needs on Emerging Infectious Diseases.
Research Topic
Identification and evaluation of novel inhibitors against Flaviviral proteases
Abstract
Salvatore Nieddu's research project focuses on the development of inhibitors for Flavivirus proteases, with a specific emphasis on West Nile Virus (WNV) and Dengue Virus (DNV). The urgency of this research is underscored by the significant global health impact of these viruses, which cause severe endemic and epidemic infections, and the current lack of approved specific antiviral drugs, despite available vaccines for some Flaviviruses.
The primary target is the viral NS2B-NS3 protease, identified as a highly attractive target for antiviral development. NS3 is a multifunctional protein, possessing ATPase, helicase, and (when associated with NS2B) protease activities, with a highly conserved catalytic triad crucial for the viral replication cycle.
The project's methodology is structured in several phases:
In silico screening using bioinformatics methods like molecular docking to identify potential NS2B-NS3 protease inhibitors, selecting compounds with optimal binding affinity.
In vitro testing (biochemical assays) to evaluate the inhibitory activity of identified compounds. This involves the production and purification of recombinant viral proteins and the development of FRET-based functional assays to measure protease activity. IC50 values will be determined for the most promising compounds.
In vitro testing (cellular assays) to assess the antiviral activity and cytotoxicity of the compounds on WNV and DNV-infected cells, determining EC50 and CC50 values. An effective compound should demonstrate an EC50 significantly lower than its CC50.
The overall aim is to provide a crucial tool to combat future Flavivirus epidemics and, given the high conservation of the protease, to expand knowledge towards identifying broad-spectrum antiviral drugs active against other viruses within the same family.
Publications