Projects

New drugs for HIV prevention: novel inhibitors against an essential HIV target

Antiretrovirals can be effective for preventing the sexual transmission of HIV. However, drugs now being applied to prevention are from the same drug classes used for HIV therapy, which could lead to the transmission of drug resistant strains. Consequently, there is an immediate need for novel drug classes specifically for HIV prevention.

We have initiated a drug discovery program targeting HIV-1 reverse transcriptase (RT) to find compounds that inhibit the target protein in novel ways. We are using an innovative and validated paradigm for drug discovery called fragment-based drug design (FBDD) that uses very small compounds called “fragments” to find inhibitors with novel mechanisms of action. Using FBDD means screening far fewer compounds than conventional drug screens since fragments are so small and can better probe the viral target. Fragments can then be developed into more potent and efficient drugs.

Our initial screen has identified five promising fragments that inhibit HIV-1 reverse transcriptase, where three fragments use mechanisms that are distinct to drugs in the clinic.

The aim of this study is to progress one of these fragments into more potent RT inhibitors or drug leads. Compounds that are structurally related to fragment hits will be evaluated for their ability to bind and inhibit wild-type and drug resistant RT, as well as inhibit HIV-1 replication. This study will identify leads from fragments for development of a novel class of RT inhibitor for specific use in HIV prevention.

Collaborators

  • David Chalmers, Monash Institute of Pharmaceutical Sciences, Melbourne
  • Martin Scanlon, Monash Institute of Pharmaceutical Sciences, Melbourne
  • Jamie Simpson, Monash Institute of Pharmaceutical Sciences, Melbourne
  • Nicolas Sluis-Cremer, University of Pittsburg, USA
  • Eddy Arnold, Rutgers University, New Jersey, USA

Funding

Percy Baxter Charitable Trust, managed by Perpetual Trustees New drugs for HIV prevention: novel inhibitors against an essential HIV target FR2013/0422

NHMRC Project Grant 1064900 Novel class of HIV reverse transcriptase inhibitor for HIV prevention

Health Issue

Contact Details

For any general enquiries relating to this project, please contact:

Professor Gilda Tachedjian

Head of Life Sciences; Head of Tachedjian Laboratory (Retroviral Biology and Antivirals)

Telephone

+61392822256

Email

gilda.tachedjian@burnet.edu.au