Targeting the HIV-1 Nucleocapsid Protein to fight .. (THINPAD)
Targeting the HIV-1 Nucleocapsid Protein to fight Antiretroviral Drug Resistance
Date du début: 1 sept. 2013,
Date de fin: 31 août 2016
AIDS is one of the most serious pandemic diseases of the modern era. Although current therapies based on targeting key processes of the HIV replication cycle are potent and selective, several clinical failures are recorded due to the emergence of drug resistance. Hence, there is an urgent need for novel drugs and alternative therapeutic strategies.The objective of the THINPAD proposal is to discover and develop novel anti-HIV agents targeting the HIV nucleocapsid protein(NC), which is one of the most conserved sequence within HIV strains and is highly required for HIV replication, being therefore a primary target to overcome antiretroviral drug-resistance. The proposal originates from the successful FP6 TRIoH project and presents a multidisciplinary approach to develop anti-HIV drugs, ready for early clinical trials, that could be resistant to viral mutation since targeting a highly conserved sequence.The consortium consists of experts in the anti-HIV field which have an extensive expertise in targeting NC. Partner 1 has studied the NC dynamics and discovered small molecule NC modulators by in silico approaches. Partner 2 has developed biophysical methods to monitor the NC functions and the interaction with small molecules. Partner 3 developed a complete approach of biochemistry-, retrovirology- and microscopy-based techniques to monitor NC during HIV assembly, maturation and reverse transcription. Partner 4 is a SME founded by scientists who participated in the development of Raltegravir, which will have a leading role in the project together with Partner 5 (SME) by driving the discovery phase and pre-clinical investigation, favouring the translation of results into innovative applications for health.It is worth noting that the consortium already possesses small molecules endowed with low-micromolar inhibitory activity in cell against HIV and active against resistant strains. Notably, these molecules interact with the NC but not with the usual anti-HIV targets
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