I joined the Frieman lab as a post-doctoral fellow in 2016 having completed a PhD at University College London. My PhD involved study of the IFITM proteins which are cellular antiviral factors that inhibit cell entry of numerous viruses. My interests lie in developing better understanding of how viruses and their hosts interact and counteract each other with a view to using this knowledge to develop medical interventions. The development of host-directed antivirals would help to circumvent issues around the evolution of viral resistance. Moreover, host-directed therapies may have broad-spectrum activity and the development of broad-spectrum antivirals would put us in a better position to deal with novel emerging pathogenic viruses such as SARS-CoV-2, the causative agent of COVID-19.
In the Frieman lab I extended these interests by developing a yeast-based screening system to identify eukaryotic factors that have genetic interactions with viral proteins, focusing on coronaviruses and influenza as these viruses pose great risk for pandemic spread. That work identified a novel host factor in replication of MERS-CoV, SIRT1. The screen was also used to identify the mammalian SKI complex as a proviral factor in replication of various RNA viruses. The SKI complex is an RNA helicase complex involved with cellular RNA metabolism, its removal from cells inhibits replication of both influenza and coronaviruses, suggesting it may have broad roles in viral replication. In collaboration with labs in the University of Maryland, School of Pharmacy, we have developed a series of chemical compounds that interact with the SKI complex and inhibit replication of influenza, coronaviruses and the filoviruses Ebola and Marburg. On-going work is aimed at developing a detailed understanding of how disruption of the SKI complex inhibits replication of these diverse viruses and further improving the activity of our chemicals with the aim of developing broad-spectrum antivirals.
Links
Twitter - @StuartMWeston
YouTube – Diaries of a Coronavirologist https://www.youtube.com/channel/UCQGv0nI5XuM0RT_E0aBurKQ
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