Probe Used to Determine Efficacy, Toxicity of HIV Drugs
A biomedical engineer has developed a molecular probe that can simultaneously detect the presence of HIV-1 protease and toxicity levels of chemical compounds used to combat the deadly virus that causes AIDS. The probe can be used to investigate the efficacy and efficiency of HIV drugs, some of which are so toxic that many patients elect to stop treatment.
This image illustrates HIV-1 protease activity detected by Sha Jin's molecular probe.
Although it is currently incurable, HIV can be controlled by anti-HIV drugs, which suppress or inhibit virus replication in patients. Currently, treatment of HIV infection depends upon a strategy called highly active antiretroviral therapy, in which drugs that inhibit HIV-1 protease – a family of enzymes essential for the life cycle of HIV – are combined with drugs that suppress virus replication. Although the therapy has reduced mortality, it has side effects. A quarter of patients with HIV stop therapy within the first year due to symptoms related to its high toxicity.
To address this issue, Jin created a screening system by applying fluorescent proteins, one green and one red, to generate Förster resonance energy transfer signals responsive to HIV-1 protease inhibition and activity. Förster resonance energy transfer is a mechanism of energy transfer between a donor and receptor chromophore, the part of a molecule that is responsible for its color. The energy transfer prompts reactions from cells in the form of color. In the absence of protease inhibitors, the researchers observed green and yellow cells. When protease inhibitors were added to cells, they showed a red color.
"We confirmed that compounds nelfinavir and lopinavir were toxic to cells, since many healthy cells died after two days incubation," Jin said. "Indinavir, sequinavir, and ritonavir showed less toxicity."