Science Translational Medicine: New Drug Blocks Anchoring of HIV to Host Cells

A new drug based on a natural compound produced by the human body halts one of the earliest stages of HIV infection, reports a new study in the journal Science Translational Medicine. The drug may be able to slow down emerging resistance of the virus to antiretroviral drugs, a growing problem worldwide.

Called VIR-576, the drug interacts with HIV’s ability to insert the “sticky” end of its outer membrane—the fusion peptide—into the host cell at the start of infection. This ability to block fusion peptides makes VIR-576 very different from other HIV drugs.

“To the best of our knowledge, this is the first time that a derivative of a natural compound shows antiviral efficacy in a clinical study,” said lead author Frank Kirchhoff, professor at the Institute of Molecular Virology at the University Hospital of Ulm in Germany.

The findings reported in the 22 December issue also provide evidence that inhibiting fusion peptides can stall HIV replication in humans by preventing direct interaction between the virus and host cells.

However, this new drug does have some drawbacks; because VIR-576 is a peptide and must be given through injections, it will be costly and inconvenient to use. This has prompted Kirchhoff and colleagues to start hunting for a small molecule that works just like VIR-576, but with the advantage that it could be made cheaply and given orally.

“The preliminary results are promising but these studies are time-consuming and it’s too early to say whether they will lead to products suitable for clinical application,” said Kirchhoff.

Fusion peptides are also used by most enveloped viruses, including influenza, mumps, measles, Hepatitis B, Hepatitis C, Ebola, and SARS viruses. So the discovery that VIR-576 can effectively fight early HIV infection suggests that it may be possible to develop similar inhibitors against other dangerous viruses. Moreover, fusion peptides can hardly tolerate genetic changes, so it will likely be difficult for the virus to develop resistance to VIR-576.

In the phase I/II trial of VIR-576, 18 HIV-infected volunteers were treated for 10 days with three different doses of the new drug, which was the first antiretroviral drug they received.

The authors note that the volunteers did not stop their current therapy to participate in the trial and that VIR-576 does not bear a risk for inducing cross-resistance to other drugs. The researchers found that the drug was well tolerated and reduced the average viral load (a measurement of the amount of active HIV in the blood) by 95%, when taken at the highest dose.

Links

Read the abstract for “Short-Term Monotherapy in HIV-infected Patients with a Virus Entry Inhibitor Against the gp41 Fusion Peptide.”

Watch an informal interview with Frank Kirchhoff.

Visit Science Translational Medicine