On Sept. 15, 2020, the U.S. Food and Drug Administration (FDA) awarded a $5.4 million research contract to the University of Liverpool and global partners to sequence and analyze samples from humans and animals to create profiles of various Coronaviruses.

The emergence of SARS-CoV-2 in 2019 and the associated COVID-19 pandemic, and prior SARS-CoV and MERS-CoV outbreaks, demonstrate the significant threat posed by coronaviruses. Several vaccines and antiviral therapies are being utilized against SARS-CoV-2, but there is an urgent need to support development and evaluation of additional medical countermeasures (MCMs).

In this Medical Countermeasures Initiative (MCMi) regulatory science project, the University of Liverpool (ULIV) and international partners will analyze SARS-CoV-2 (including variants of concern, such as the Delta variant), SARS-CoV, and MERS-CoV clinical samples, collected through global partnerships, to better understand coronavirus evolution and virulence, characterize host-pathogen interactions and immunity, and identify biomarkers of disease progression and severity. Through the sequence analysis of current and ongoing collection of samples from humans and animals, this project will help inform the real-time performance of molecular-based diagnostics (e.g., genetic drift that may evade the current molecular diagnostic tests).

This project also has the potential to provide a better understanding of vaccine and therapeutic targets, including biomarkers of protection, potential development of antiviral resistance, and host-directed therapeutics for a broad range of coronaviruses. The pattern of severe disease in COVID-19 is similar to both MERS and SARS, particularly with regard to an enhanced and overt host inflammatory response. This will be investigated and compared in human and animal models. Identification of potentially common pathways would provide necessary information for development of host-directed MCMs.

The project will also examine in vitro models of coronavirus infection, including microphysiological systems (MPS) such as human organs-on-chips, to elucidate how these models compare to in vivo responses in animal models and humans. Ultimately, these in vitro models will result in enhanced MCM screening methods.