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EASTBIO COVID-19 Drug Discovery: Discovering Antiviral Compounds that Inhibit SARS-CoV-2


   School of Biology

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  Dr C Adamson, Prof T K Smith  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

BACKGROUND

The COVID-19 pandemic is a global health challenge. Despite successful vaccine development and ongoing vaccine rollout, antiviral drugs are required for patients that succumb to serious disease.

The purpose of this PhD project is to identify novel compounds that inhibit SARS-CoV-2 replication, that can be (i) used as chemical tools to further understand SARS-CoV-2 replication and host-cell interactions and (ii) further developed into SARS-CoV-2 antiviral drugs to treat COVID-19.

The Adamson lab has developed and validated a cell-based assay to screen compound libraries to identify hit compounds with anti-SARS-CoV-2 activity. The assay principle is inhibition of SARS-CoV-2-induced cytopathic effect. Addition of a compound that inhibits SARS-CoV-2 replication, will prevent cytopathic effect, leaving healthy cells which convert a cell viability reagent to a measurable fluorescent signal to indicate a hit antiviral compound.

The project will utilize an innovative iterative screening approach. Prior to the project start, a 5K Diversity Compound Library has been screened using our cell-based SARS-CoV-2 assay and hit compounds identified. The Diversity library is a subset of the larger 125K Compound Cloud Library held by BioAscent, a leading drug discovery company in Scotland, UK. During the PhD, hits identified in the primary screen will be further investigated and validated hits used to conduct similarity searches to identify related chemical structure/profiles within the larger Compound Cloud, to facilitate further rounds of iterative-focused screening using small custom-libraries based around each validated hit. The objective is to identify novel potent selective compounds with structure-activity-relationship (SAR) data that will be progressed to mechanism of action studies.

Our assay has the potential to identify a diverse range of novel compounds with different mechanisms of action. Hit compounds could belong to traditional drug classes such as entry, protease or polymerase inhibitors. Alternatively, novel drug classes targeting other SARS-CoV-2 proteins and virus-host interactions could be identified.

During this PhD, the candidate will gain training in both biology and chemistry disciplines. Biological skills will include training to work with the SARS-CoV-2 virus in the biosafety level 3 laboratory (BSL3) at St Andrews, together with skills in virology, cell culture and a range of biochemistry/cell biology/molecular techniques. Chemical skills will include computational chemistry, medicinal chemistry and SAR studies. Overall, the candidate will acquire a broad range of skills in the field of drug discovery.

Supervisors Dr Catherine Adamson and Professor Terry Smith have a strong track record in multiple aspects of infectious disease drug discovery research.

HOW TO APPLY

Application instructions can be found on the EASTBIO website- http://www.eastscotbiodtp.ac.uk/how-apply-0

1)     Download and complete the Equality, Diversity and Inclusion survey.

2)     Download and complete the EASTBIO Application Form.

3)     Submit an application to St Andrews University through the Online Application Portal

Your online application must include the following documents:

-         Completed EASTBIO application form

-         2 References (to be completed on the EASTBIO Reference Form, also found on the EASTBIO website)

-         Academic Qualifications

-         English Language Qualification (if applicable)

Unfortunately due to workload constraints, we cannot consider incomplete applications. Please make sure your application is complete by Monday 5th December 2022.

 

 

CONTACT

Queries on the project can be directed to the project supervisor.

Queries on the application process can be directed to Jess Fitzgerald at [Email Address Removed]

UKRI eligibility guidance: Terms and Conditions: View Website International/EU: View Website


Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership.
This opportunity is open to UK and International students and provides funding to cover stipend at UKRI standard rate and UK level tuition fees. The University of St Andrews will cover the Home-International fee difference.

References

1. Vasou, A., Paulus, C., Narloch, J., Gage, Z., Rameiz-Welti, M-A., Eleouet, J-F., Nevels, M., Randall, RE,. Adamson CS. Modular cell-based platform for high throughput identification of compounds that inhibit a viral interferon antagonist of choice. Antiviral Res, 2018. 150: p. 79-92.
2. Cockram PE, Dickie EA, Barrett MP, Smith TK (2020) Halogenated tryptophan derivatives disrupt essential transamination mechanisms in bloodstream form Trypanosoma brucei. PLoS Negl Trop Dis 14(12): e0008928. https://doi.org/10.1371/journal.pntd.0008928
3. Murgatroyd C., Pirrie, L., Tran, F., Smith, TK, Westwood, NJ., Adamson CS. Structure-activity relationships of the human immunodeficiency virus type 1 maturation inhibitor PF-46396. J. Virol, 2016, 90:p8181-97.

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