Professor Mark Harris, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds

I graduated from Plymouth Polytechnic in 1983 with a degree in Biological Sciences, before PhD study with Ron Hay at the Institute of Virology in Glasgow on adenovirus DNA replication.  After a post-doctoral position studying baculoviruses with Bob Possee at the NERC Institute of Virology in Oxford I moved back to Glasgow to the Department of Veterinary Pathology to study the HIV-1 Nef protein with Jim Neil.  I was awarded an MRC AIDS Directed Programme Senior Fellowship in 1994, and subsequently took up a Lectureship at the University of Leeds in 1997 where I started to develop research interests in hepatitis C virus (HCV), funded by the MRC, BBSRC and Wellcome Trust.  In 2011 I was awarded a Wellcome Trust Senior Investigator Award.

My research has focussed on HCV, but over recent years I have diversified to encompass as Chikungunya virus, Ebola virus, hepatitis E virus and SARS-CoV-2.  My laboratory studies mechanisms of genome replication, virus assembly and host cell-virus interactions, and applies a combination of molecular, cellular and structural biology approaches. In parallel I maintain an interdisciplinary theme of antiviral drug development: firstly, in collaboration with colleagues in Brazil (Carol Jardim, Uberlandia and Paula Rahal, Sao Paolo) to investigate the potential of natural products as inhibitors of viruses including HCV, Chikungunya and SARS-CoV-2. Secondly, in collaboration with Leeds chemists Colin Fishwick and Martin McPhillie, we use in silico drug design to develop novel antiviral agents targeted to a range of viruses: HCV, Ebola, Chikungunya and SARS-CoV-2.

In my talk I will focus on HCV direct acting antivirals (DAA), in particular those targeted at the multifunctional NS5A protein.  These compounds have extraordinary potency, minimal side effects, and are a key component of the combination DAA therapy that has revolutionised HCV treatment, but as yet their mode of action remains obscure.

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