MRC DiMeN Doctoral Training Partnership: Therapeutics for Middle Eastern Respiratory Syndrome

Description

The overall aim of this project is to develop therapeutic interventions for Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The work is in collaboration with Infex Therapeutics and comes with an enhanced stipend.

Background: Emerging pandemics are a constant threat, causing widespread morbidity, mortality and economic cost. The COVID-19 pandemic resulted in 7M deaths (WHO) and cost of $12.5 trillion (IMF) globally. Middle Eastern respiratory syndrome coronavirus (MERS-CoV) is an emerging threat with pandemic potential. There are good vaccines and therapeutics now for SARS-CoV-2 but there is little available for MERS-CoV. The COVID-19 pandemic highlighted the need for a range of therapeutics to fill the gap before deployment of specific vaccines and for treating those where vaccines are ineffective. MERS-CoV is a zoonotic virus responsible for outbreaks of severe respiratory disease in the Middle East. Case fatality rates can be up to 35%. Transmission to humans is largely from camels but human-to-human transmission has been reported. MERS-CoV is a containment level 3 pathogen and so its study is slowed by the requirement for dedicated facilities. The development of rapid in vitro screens based on non-infectious replicons will speed up the development of drug interventions before more detailed testing in higher containment. The development of efficacious drugs is critical and novel. Mutation and evolution of MERS-CoV to be more transmissible to and between humans poses a considerable pandemic threat. The identification of therapeutics to combat these agents is therefore extremely timely.

Aims:

This project will develop novel therapeutics for MERS-CoV by:

1. developing in vitro and in vivo model systems for studying MERS-CoV

2. To evaluate the efficacy of existing and developing therapeutics either alone, or in combination against MERS-CoV

3. To derive greater insights into the replication and pathogenesis of this virus

Experimental approach: Non-infectious in vitro replicon systems will be developed for MERS-CoV. Similar systems developed by the second supervisor for other viruses have proven effective and can be used in conventional laboratories. This replicon will be used to study replication and screen existing antiviral compounds and those developed by the industrial partner. Effective compounds or combinations will be tested in vitro against live MERS-CoV. A preclinical mouse model will be developed and used to study pathogenesis and evaluate compounds identified in the in vitro screens. In addition, MERS-CoV exposed to compounds will be evaluated for sequence mutations and resistance.

The student will receive extensive training in virology, cell biology, in vivo infection models, pathology, next gen sequencing and the development of therapeutics, as well as the experience of working in a dynamic commercial environment.

Further information:

X: @molvirol

https://www.liverpool.ac.uk/people/james-stewart

https://scholar.google.com/citations?hl=en&user=nUQLh30AAAAJ&view_op=list_works&pagesize=100

https://www.liverpool.ac.uk/infection-veterinary-and-ecological-sciences/research/groups/respiratory-and-emerging-viruses/about/

https://www.vet.uzh.ch/de/fakultaet/frauen/kipar.html

iCASE industrial partner web link: https://www.infextx.com/

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of-the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, training opportunities or internships in science policy, science communication and beyond. Further information on the programme and how to apply can be found on our website:

https://www.dimen.org.uk/