###Targeting HIV-1 drug resistance using artificial intelligence predictions
Project ID: 2228bd1116 (You will need this ID for your application)
Research Theme: Artificial Intelligence and Robotics
UCL Lead department: Division of Medicine
Lead Supervisor: Edith Chan
Project Summary:
Why this research is important? The rapid and high mutation frequency of HIV-1 has necessitated continual improvement of antiretroviral therapies. To date, around 50 drugs against various proteases, integrases, and reverse transcriptases have been FDA-approved. Novel approaches and new viral targets are essential to combating resistance. We propose using machine learning and modelling techniques and large-scale multi-omics data to understand and predict the mutations and to lead to the design of new potential drugs. The proposed compounds will be synthesized and tested in anti-HIV assays. This work can have wider impact in aiding the design of capsid targeting drugs against other viruses.
What you will be doing? The HIV-1 capsid has emerged as the next target of novel antiretrovirals due to its essential roles in both the early and late stages of the viral replication cycle and an extensive database of HIV-1 capsid sequences is available. The capsid core is formed of pentameric and hexameric subunits assembling to make the mature viral capsid. Interestingly, there are at least five potential drug binding sites on the capsid. One of them is formed at the interface of the hexamer. Blocking any of these binding sites could disrupt the formation of the capsid. Analysis of the HIV-1 clades? binding sites and the interactions between protein-inhibitors will be carried out using bioinformatics, machine learning, and modelling techniques. We have already designed and synthesised potent inhibitors of the PF (CPSF6) binding site of HIV-1 capsid. Structure activity relationships will be derived and, based on the results of these analyses, new compound ideas can be proposed and hypotheses tested, which is the final goal of this project.
Who we are looking for? Keen scientist who is self-motivated and independent. They are interested in interdisciplinary project.