A variety of molecules in human blood have been implicated in the inhibition of HIV-1, the researchers noted. However, it had remained elusive which circulating natural compounds are most effective in controlling viral replication in the body.
In the new study, the researchers sifted through a comprehensive library of small peptides that had been filtered from the blood of patients with chronic kidney failure during dialysis, in search of those with anti-HIV activity. After sorting the more than one million blood peptides into 300 fractions, they focused on one that blocked HIV without toxic effects on cells.
Further examination revealed VIRIP as the active ingredient. A synthetic version of the peptide maintained its anti-HIV activity, excluding the possibility that some other factor was responsible.
VIRIP specifically targets a conserved region in the HIV-1 transmembrane glycoprotein known as "gp41 fusion peptide." This peptide, which is normally buried in the viral envelope, becomes exposed during the process of viral entry and makes the first direct contact between the viral particle and host cell.
Thus, they showed, VIRIP plays an essential role in the ability of HIV to fuse with and infect its host's immune cells. That unique underlying mechanism allowed the inhibitor to remain effective against viral strains that are resistant to other antiretroviral drugs, they found.
"Our data support the possibility that VIRIP may contribute to controlling HIV-1 replication in infected individuals and that derivates thereof are highly suitable for development of a new class of HIV-1 inhibitors targeting the highly conserved gp41 fusion protein," the researchers concluded.
There are now some 20 different HIV drugs in use, Kirchhoff said. However, the treatments all fall into one of four categories based on their modes of action, and a growing number of HIV strains are becoming drug resistant.