Retroviral Biology and Antivirals Group

Head: Professor Gilda Tachedjian

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Overview

Our overall goal is to identify and develop effective antiviral strategies to prevent and control pathogens, including HIV.

We achieve this through discovering, developing and elucidating the mechanism of action of novel antivirals for HIV treatment and prevention, and by understanding the role of the genital microbiota and their metabolites on adverse sexual (e.g. HIV) and reproductive health outcomes.

We undertake fundamental studies to understand the biology of viruses and their interaction with host restriction factors.

Objectives

  • Elucidate the role of the vaginal microbiota and their metabolites in adverse sexual (i.e. HIV) and reproductive health outcomes
  • Develop a new drug class for HIV treatment and prevention
  • Understand virus-host interactions

Highlights

  • Discovery of a vaginal microbiota metabolite with anti-inflammatory effects on cervicovaginal epithelial cells that could help prevent HIV
  • Discovered that bats encode a diverse number of APOBEC3 genes, a major class of intrinsic antiviral genes
  • Discovery of small chemical building blocks (fragments) with mechanism of action distinct to HIV reverse transcriptase inhibitors used in the clinic
  • Discovery of a vaginal microbiota metabolite, lactic acid, that is more potent than acidity alone in killing HIV
  • Identification and characterisation of endogenous retroviruses in bats
  • Structure-activity relationship studies of dendrimer microbicides against HIV and genital herpes revealing that the dendrimer SPL7013 is the most potent against both viruses
  • Successful completion of a phase I dendrimer microbicide, SPL7013 Gel (VivaGel) clinical trial in healthy women demonstrating retention of HIV-1 and HSV-2 inhibitory activity.
  • Discovery of a novel mutation, N348I in the C-terminal domain of the HIV reverse transcriptase which confers resistance to zidovudine and nevirapine
  • Demonstration that potent members of a class of HIV-1 drugs called non-nucleoside reverse transcriptase inhibitors block the production of viral particles by increasing the processing of viral polyproteins inside the host cell

Projects