Project Lead(s): Ian Tietjen
Antiretroviral therapy (ART) has significantly reduced HIV-1 morbidity and mortality.
However, fewer than 50% of HIV-1 patients have access to ART in many low- and middle-income countries (LMICs), and the therapy is expensive and can have adverse side effects.
Drugs that are locally available and target additional aspects of the HIV life cycle not addressed by current therapies are urgently needed.
Viroporin blockers like amantadine are historically proven antivirals, but virtually no viroporin blockers exist for viruses that disproportionately affect LMICs.
The team sought to screen natural products to find these viroporin blockers that could be beneficial against HIV-1.
Using electrophysiology (EP) and cell assays, they have discovered natural products from Southeast Asia and elsewhere that act on Vpu, an ion channel, or viroporin, encoded by HIV-1.
Subsequently, the team aimed to explore the effects of natural products and other potential antiviral agents against aspects of HIV replication and/or other viruses, like influenza, that also affect LMICs.
A potent synthetic Vpu inhibitor was characterized using an in vitro viral replication assay and found that SM111 inhibits replication of wild-type HIV-1 (EC50 = 25 µM).
The project achieved its goal of identifying novel Vpu inhibitors from natural products.
Knowledge was disseminated in publications and conferences.
The team does not plan to apply for Phase II Transition To Scale funding, as additional research is required before clinical trials or commercialization can be undertaken.
In the interim, the team will continue to engage non-profit funding agencies to support this work.
Funds were leveraged as follows: $15,000 from industry sources to perform pre-clinical studies on a Vpu inhibitor; $60,000 from the International Development Research Centre (IDRC); $10,000 from Simon Fraser University; and a $2,500 Canadian Institutes of Health Research (CIHR) travel award.