HIV left out in the cold

Anti-viral agents launch a two-fronted attack on HIV.

A new approach to tackle HIV infection which could help against drug resistant strains is being pioneered by scientists from the University of Maryland, US.

Lai-Xi Wang and colleagues have made an antiviral agent with two possible modes of action. Their concept involves combining a modified T20 peptide with a group which will be recognised by human antibodies and start an immune response. T20 can powerfully inhibit HIV entry into cells and has recently been approved for use by the US Food and Drug Administration (FDA). The group that T20 combines with mimics the α-Gal epitope, a molecule present on the surface of many mammalian cells responsible for organ rejection after transplant surgery.

HIV enters cells, and causes infection, by a mechanism involving binding to the cell surface, then penetrating the cell membrane and off-loading the virus into the cell. T20 stops the penetration stage, effectively leaving the virus out in the cold, with the α-Gal epitope left dangling. Anti-Gal antibodies circulating in the blood then recognise and attack the tagged HIV particles. Wang’s anti-viral agent shows good anti-HIV activity even without human antibodies present.

Commenting on the work, Peter Wipf, a bioorganic chemist from the University of Pittsburgh, US, said ’the current surge in Phase III clinical studies and FDA approvals of immunoglobulin-based therapeutic agents illustrates the great promise of selective targeting mechanisms in drug discovery. This study by Wang and colleagues is relevant to these efforts, since it can provide the basis for new antibody-mediated lysis of HIV particles and HIV-infected cells. The synthetic scope of their work is impressive’.

In the future, Wang hopes that ’if proven successful in vivo, [this work] would lead to a new class of anti-HIV drug for the treatment of HIV/AIDS’.

Steven Evans