BrainMap

Mrs. Alina Bora

Ph.D.

Senior researcher - INSTITUTUL DE CHIMIE "CORIOLAN DRĂGULESCU"

Researcher

Web of Science ResearcherID: AAW-8757-2020

Expertise & keywords

Indentification of first in class chemical scaffolds against Hepatitis C Virus NS2 cysteine protease Call name: P 3 - SP 3.2 - Proiecte ERA.NET - COFUND
ERA.NET.RUS PLUS-HCVCYSPROT 2016 - 2018

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO); INSTITUTUL DE CHIMIE (RO)

Affiliation: INSTITUTUL DE CHIMIE (RO)

Project website: http://www.hcvcysprot.com

Abstract:

Hepatitis C Virus (HCV) infects 120-130 million people worldwide. Most of cases evolve to chronicity inflicting liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. The standard therapy consisting of interferon alpha and ribavirin has been recently complemented by direct acting antivirals (DAA) which

target NS3 protease, NS5A protein and NS5B polymerase. The FDA approved DAAs and the others in advanced clinical trials increase significantly the sustained virological response and moreover there is proof of concept for an interferon free therapy. However, the new DAAs do not provide full genotype coverage and there are still significant side-effects. Thus, there is an unmet need for new antiviral strategies. The majority of the present antiviral therapies have focused on three major targets: NS3 protease, NS5B polymerase and NS5A protein. A very attractive target is represented by the second viral protease, NS2 cysteine autoprotease. NS2 protease is crucial for polypeptide processing and viral replication. Up to date, the identification of NS2 protease inhibitors was hampered by the scarce of robust enzymatic assays which might be automated for highthroughput screening campaigns. The aim of the project is to identify first in

class chemical scaffolds with inhibitory activity for HCV NS2 protease. To accomplish that, we will take

advantage of a unique cell based NS2 enzymatic assay to perform the primary screening. The resulted hits will be confirmed by secondary screenings in Hepatitis C Virus cell culture system. The mode of action will be confirmed by drug resistant mutations identification in HCVcc and in “in vitro”biochemical assays for NS2 protease activity. The validated scaffolds will be derivatized for structure –activity relationship (SAR) studies.

Innovative strategies for in silico modelling of promiscuous compounds evaluated in high-throughput screening Call name: Projects for Young Research Teams - RUTE -2014 call
PN-II-RU-TE-2014-4-0422 2015 - 2017

Role in this project:

Coordinating institution: INSTITUTUL DE CHIMIE

Project partners: INSTITUTUL DE CHIMIE (RO)

Affiliation: INSTITUTUL DE CHIMIE (RO)

Project website: http://www.chembioinf.ro/en/Grants/

Abstract:

Today, high-throughput screening (HTS) has become the standard procedure to test large libraries of compounds against biological targets in early-stage drug and agrochemical discovery. It is now recognized that HTS results are heavily affected by errors due to physico-chemical and biological properties of the molecules embedded in the screening libraries. Such compounds interfere with the assays signal-detection method (fluorescent and reactive compounds, luciferase inhibitors) or form functional aggregates in the assay medium. Consequently, nonspecific or apparent activity against various, unrelated proteins in many HTS assays, generate false-positive results. The aim of this project is to develop a comprehensive methodology to predict promiscuous compounds (frequent hitters, FHs). In this endeavor we will use PubChem Bioassay (>1 million assays), a series of molecular/fragmental descriptors and state-of-the-art modelling algorithms to explore prediction models for highly reactive compounds, fluorescent compounds, luciferase inhibitors and functional aggregators. The most efficient models will establish a first integrative approach to predict FHs, which will further assist decision-making in HTS and accelerate chemical developments. Thus, the current project offers an unprecedented, systematic exploration of the limits of current-state cheminformatics tools to pursue the prediction of FHs.

FILE DESCRIPTION	DOCUMENT
List of research grants as project coordinator or partner team leader
Significant R&D projects for enterprises, as project manager
R&D activities in enterprises
Peer-review activity for international programs/projects