Discovery and development of antiviral nucleosides: The story of Remdesivir (GS-5734), a broad spectrum antiviral agent for the treatment of Ebola
Event Details
- Date:
- Monday, 30 September 2019
- Time:
- 1:00 pm - 2:00 pm
- Room:
- Seminar Room
- UQ Location:
- Australian Institute for Bioengineering and Nanotechnology (St Lucia)
- URL:
- https://scmb.uq.edu.au/event/session/6074
- Event category(s):
Event Contact
- Name:
- Mrs Brianne Mackinnon
- Phone:
- 32595
- Email:
- research@scmb.uq.edu.au
- Org. Unit:
- Chemistry and Molecular Biosciences
Event Description
- Full Description:
- Established in 1982, the Bertram Dillon Steele Lecture commemorates UQ’s founding Professor of Chemistry, Bertram Dillon Steele, one of the original four professors appointed to the University.
This year's lecture, Discovery and development of antiviral nucleosides: The story of Remdesivir (GS-5734), a broad spectrum antiviral agent for the treatment of Ebola, will be presented by Dr Richard Mackman, Vice President of Medicinal Chemistry at Gilead Sciences:
Many antiviral drugs ranging from acyclovir for the treatment of Herpes, to more recent antiviral therapies that combine drugs to treat HIV or cure Hepatitis C have been approved by regulatory agencies. Nucleoside-based inhibitors of viral polymerases, an enzyme essential for the replication of the viral genome, are frequently the backbone of antiviral treatments. There are however significant challenges to the development of nucleoside therapeutics including efficient delivery to the infected tissue in humans, intracellular activation of prodrugs, and host-viral selectivity. Case studies from HIV, HCV and RSV antiviral nucleoside programs highlight these challenges and provide the foundational background for the discovery story of Remdesivir (RDV, GS-5734) for the treatment of Ebola.
Remdesivir is a prodrug of a novel adenosine analog, and a rare example of a broad spectrum antiviral agent with the potential to treat multiple RNA viruses including filoviruses, pneumoviruses, flaviviruses, paramyxoviruses and coronaviruses. Effective treatments for emerging viruses with high outbreak potential are severely limited, a realization that reached global prominence during the 2013-16 Ebola virus (EBOV) outbreak that claimed >11,000 lives. At the time of this outbreak, a focused screening effort in collaboration with USAMRIID and the CDC identified a nucleoside lead that was subsequently optimized to the prodrug RDV. Mechanism studies support RDV as being a delayed chain terminator of Ebola RNA synthesis. In EBOV-infected monkeys, once daily IV administration initiated on day 4 post infection demonstrated 100% survival in an otherwise lethal challenge model. Efficacy has also been observed in animal models of Marburg, Nipah and MERS-Coronavirus infections supporting the broader potential for RDV use in the treatment or other RNA viruses. RDV has been provided for compassionate use in the latest DRC Ebola outbreak and is the only small molecule antiviral being investigated in an ongoing Ebola randomized controlled trial.
Directions to UQ
- Google Map:
-
- Directions:
- St Lucia Campus | Gatton campus.
Event Tools
Share This Event
Print
Email
Share
