Objective
Virus infections are one of the leading causes of morbidity and mortality worldwide. In particular, two viruses, which have a severe global impact, represent a major threat for the Uzbekistan health care system: the hepatitis C virus (HCV) and the human immunodeficiency virus (HIV). HCV is a major human pathogen which has infected an estimated 3% of the population worldwide and around 6.5% of the Uzbek population (hence more than the double of the worldwide proportion).HIV is the etiological agents of the acquired immune deficiency syndrome (AIDS), a pandemic which has infected more than 42 million people worldwide and has a growing diffusion in Asia, clearly representing a threat also for the Uzbek people. The present research project is aimed to identify new molecules, either from natural or synthetic origin, that may block the replication of these two viruses through the inhibition of the virus-coded polymerizes, the HCV RNA-dependent RNA polymerize (RdRp) and the HIV RNA- and DNA-dependent DNA polymerize, the reverse transcriptase (RT), which also shows an essential associated Ribonuclease H activity. These two viral enzymes are indispensable for their virus replicate cycle and have already been shown to be very attractive targets for drug development. To this purpose, the team partners involved in the project bring different and complementary scientific expertise which are all required to identify and develop new antiviral agents. The Uzbekistan Low Molecular Bioreg and Kazakhstan Kazbioreg teams have a long expertise history in developing medical means based both on low molecular natural compounds isolated from plant origin and on the synthesis of related synthetic derivatives. The Poland AMU-crystal team is expert in the crystallographic studies which are essential in understanding both the spatial configuration of potential inhibitors and the structural determinants which define the interaction between the target protein and the antiviral agent. The Italian UNICA enzymologist team brings the enzyme virologist expertise which is needed to screen the compounds for their antiviral activity and to determine their structure activity relationships (SAR). The project will start with the systematization and the screening of compounds with potential antiviral activity which are already available in the rich banks of molecules in both Uzbekistan Low Molecular Bioreg and Kazakhstan Kazbioreg laboratories. In particular, the compounds which will be initially tested for their anti-polymerize activity are low molecular weight natural product from Annacardeaceae, Geraneaceae, Punicaceae, Malvaceae and Euphorbeaceae, synthetic gossypol and monomeric catechin derivatives, triterpenoid-glycyrrhetic acid derivatives, anthraquinone analogs and hydroxyl- and aminophosphonates related to piper dines. The resulting SAR studies will allow to select potential scaffolds of antiviral molecules and, subsequently, synthesize new derivatives more potent and selective.
Fields of science (EuroSciVoc)
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
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Coordinator
09143 Monserrato (CA)
Italy
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.