Therapeutics for Middle Eastern Respiratory Syndrome

About the Project

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.

Funding Notes

This project is open to UK and international applicants with their own funding. Funding should cover course fees, living expenses and research expenses (bench fees).