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  MscR: Identification of effective drug combinations to inhibit SARS-CoV-2 variants of concern


   School of Cellular and Molecular Medicine

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  Dr Iart Luca Shytaj  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Keywords: Bristol, Virology, SARS-CoV-2, Antivirals

Variants of concern remain a public health threat associated with SARS-CoV-2 infection. Drug combinations are validated tools to potently inhibit replication of RNA viruses and decrease the likelihood of resistance mutations. However, few antiviral drugs have so far proved effective to treat SARS-CoV-2 and they are commonly given in monotherapy, with only scattered information available on their efficacy and toxicity in combination.

Recently, we have shown that the pharmacoenhancer cobicistat, typically used in combination with antiretroviral drugs to boost their efficacy against HIV-1, can inhibit the replication of the Wuhan SARS-CoV-2 strain in vitro and in vivo, in Syrian hamsters.

The present project will expand on these results by using scalable fusion assays and replicon models to screen effective drug combinations that can suppress viral replication across all major variants of concern. The student will be trained to use of multiple cellular models of infection and to combine virologic, biochemical, and imaging techniques for antiviral drug development.

The student will join a novel, international research group situated in the School of Cellular and Molecular Medicine at the University of Bristol. The work will be conducted in a multidisciplinary environment with great opportunities for building and expanding collaborations, including in topics relevant to the project such as immunology and biochemistry. The city is lively, multicultural, and regularly named among the best places to live in the UK.

MSc by Research (MScR) is a 1-year research degree that provides an intensive lab-based training and a preparation for PhD study.  You will carry out your studies as part of your research group – like a PhD student does.  Towards the end of the year, you write up a thesis on your research and are examined on this.  This degree suits students wanting to gain maximum research experience in preparation for PhD applications.   

We are keen to recruit a diverse range of students and to ensure our research is open to all. We particularly welcome applications from groups traditionally under-represented in life sciences research. Please check the University webpages for the current tuition fee information.  Most MScR projects also require a bench fee.  This varies depending on the research and your project supervisor can tell you the bench fee for the project. 

Please contact Dr Shytaj ([Email Address Removed]) directly for information about the project.

How to Apply

You should apply to the Faculty of Life Sciences, School of Cellular and Molecular Medicine selecting the programme Cellular and Molecular Medicine MSc by Research.

Please ensure you upload all supporting documents as per the admissions statement (which applies to both PhD and MScR programmes): PhD Cellular and Molecular Medicine | Study at Bristol | University of Bristol

Clearly indicate the supervisor's name and project title in the relevant section of the application form.

The system will not allow you to submit your application without uploading a document to the research statement section.  Where this is an optional requirement, please upload a blank Word document which is headed “No research statement required”.

Applications are accepted all year round. However, the preferred entry points for study are September / January / April / July.


Biological Sciences (4)

Funding Notes

This project is for students who can fund the project themselves; however, you are eligible to apply for a University of Bristol Think Big Postgraduate Award (https://www.bristol.ac.uk/students/support/finances/scholarships/think-big-postgraduate/) If you are a UK student from a Black background then you are eligible to apply for an Opportunity Bristol Scholarship (https://www.bristol.ac.uk/doctoral-college/prospective-research-students/funding/opportunity-bristol/)

References

1. Shytaj IL, Fares M, Gallucci L, Lucic B, Tolba MM, Zimmermann L, Adler JM, Xing N, Bushe J, Gruber AD, Ambiel I, Taha Ayoub A, Cortese M, Neufeldt CJ, Stolp B, Sobhy MH, Fathy M, Zhao M, Laketa V, Diaz RS, Sutton RE, Chlanda P, Boulant S, Bartenschlager R, Stanifer ML, Fackler OT, Trimpert J, Savarino A, Lusic M. The FDA-Approved Drug Cobicistat Synergizes with Remdesivir To Inhibit SARS-CoV-2 Replication In Vitro and Decreases Viral Titers and Disease Progression in Syrian Hamsters. mBio. 2022 Apr 26;13(2):e0370521. doi: 10.1128/mbio.03705-21.
2. Taibe NS, Kord MA, Badawy MA, Shytaj IL, Elhefnawi MM. Progress, pitfalls, and path forward of drug repurposing for COVID-19 treatment. Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666221132736.

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