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Development of antiviral peptidomimetic enzyme inhibitors


Project Description

Coronaviruses are a large group of viruses that circulate and evolve among various animals. They can cause mild human illnesses such as the common cold or more serious respiratory diseases as seen in the recent outbreaks of SARS (2002), MERS (2012), and COVID-19 (2019). There are currently no effective treatments or vaccines against these viruses and the possible emergence of even more dangerous strains in the future is a cause for great concerns.

Vaccines are generally very effective at protecting people against various viruses such as rubeola, rubella and influenza. A first vaccine against the deadly virus Ebola has recently been approved many years after the first virus outbreak reported in 1976 in the Democratic Republic of Congo. The development of new vaccines can take several years and is consequently not an option to combat new virus outbreaks. In the case of the SARS outbreak, which disappeared relatively quickly, companies abandoned the development of vaccines because of lack of patients for clinical trials. Apart for attempts to contain the spread of novel viruses by isolation measures, several pharmaceutical companies have also been trying to develop broad-spectrum antivirals, which some of them are currently undergoing clinical trials with patient infected by COVID-19.

The aim of the proposed research is to develop chemical methods, to design and prepare several peptidomimetic inhibitors of coronavirus enzymes in order to help develop broad-spectrum antiviral drugs.1,2

The successful candidate will carry out molecular modelling studies to design inhibitors based on known coronavirus enzymes and study the preparation of selected compounds. The chosen enzyme(s) will be produced within the group of Dr Deng and enzymatic assays will be developed to test synthetic molecules and our collection of natural products. We will collaborate with pharmaceutical companies once potent in vitro enzyme inhibitors have been found.

The student will be closely supervised and receive appropriate training in medicinal chemistry, molecular modelling, organic/peptide chemistry, analytical techniques and molecular biology.

Candidates should have (or expect to achieve) a UK honours degree at 2.1 or above (or equivalent) in Chemistry, Medicinal Chemistry, Pharmacy, Biochemistry, Cell & Molecular Biology along with knowledge of Organic Chemistry.

APPLICATION PROCEDURE:

• Apply for Degree of Doctor of Philosophy in Chemistry
• State name of the lead supervisor as the Name of Proposed Supervisor
• State ‘Self-funded’ as Intended Source of Funding
• State the exact project title on the application form

When applying please ensure all required documents are attached:

• All degree certificates and transcripts (Undergraduate AND Postgraduate MSc-officially translated into English where necessary)
• Detailed CV

Informal inquiries can be made to Dr Laurent Trembleau () with a copy of your curriculum vitae and cover letter. All general enquiries should be directed to the Postgraduate Research School ()

Funding Notes

This project is advertised in relation to the research areas of the discipline of Chemistry. The successful applicant will be expected to provide the funding for Tuition fees, living expenses and maintenance along with Additional Research Costs of £5,000 per annum. Details of the cost of study can be found by visiting View Website. THERE IS NO FUNDING ATTACHED TO THIS PROJECT.

References

1. K. Fan et al “Biosynthesis, Purification, and Substrate Specificity of Severe Acute Respiratory Syndrome Coronavirus 3C-like Proteinase” J. Biol. Chem. 2004, 279, 1637-1642.
2. K. Yunjeong et al “Broad-Spectrum Antivirals against 3C or 3C-Like Proteases of Picornaviruses, Noroviruses, and Coronaviruses” J. Vir. 2012, 86, 11754-11762.

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