HIV/AIDS Drug Development: Phosphorothioate oligonucleotides inhibit HIV-1 fusion by blocking gp41 core formation

AIDSWEEKLY Plus; Monday, June 19, 2006
Staff Medical Writers

According to recent research from Canada, "Several studies have shown that phosphorothioate oligodeoxynucleotides (PS-ONs) have a sequence-independent antiviral activity against human immunodeficiency virus type 1 (HIV-1).

"It has also been suggested that PS-ONs inhibit HIV-1 by acting as attachment inhibitors that bind to the V 3 loop of gpl20 and prevent the gp120-CD4 interaction."

"Here we show that PS-ONs (and their fully 2 '-O-methylated derivatives) are potent inhibitors of HIV-1-mediated membrane fusion and HIV-1 replication in a size-dependent, phosphorothioation-dependent manner," reported A. Vaillant and colleagues at REPLICor Inc. in Laval.

The authors continued, "PS-ONs interact with a peptide derived from the N-terminal heptad repeat region of gp41, and the HIV-1 fusion-inhibitory activity of PS-ONs is closely correlated with their ability to block gp41 six-helix bundle formation, a critical step during the process of HIV-1 fusion with the target cell."

"These results suggest that the increased hydrophobicity of PS-ONs may contribute to their inhibitory activity against HIV-1 fusion and entry, because longer PS-ONs (<30 bases) which have a greater hydrophobicity are more potent in blocking the hydrophobic interactions involved in the gp41 six-helix bundle formation and inhibiting the HIV-1-mediated cell-cell fusion than shorter PS-ONs (<30 bases)," researchers said.

Scientists concluded, "This novel antiviral mechanism of action of long PS-ONs has implications for therapy against infection by HIV-1 and other enveloped viruses with type I fusion proteins."

Vaillant and colleagues published their study in Antimicrobial Agents and Chemotherapy (Phosphorothioate oligonucleotides inhibit human immunodeficiency virus type 1 fusion by blocking gp41 core formation. Antimicrob Agents Chemother. 2006 Apr;50(4):1393-401).

For additional information, contact S.B. Jiang, REPLICor Inc., 500 Cartier Blvd. W, Suite 135, Laval, PQ H7V 5B7, Canada.

Publisher contact information for the journal Antimicrobial Agents and Chemotherapy is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA.

Keywords: Laval, Canada, HIV/AIDS, HIV-1 gp41, Fusion Inhibitor, Phosphorothioate Oligonucleotide, Pharmaceutical & Drug Development.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Vaillant A, Juteau JM, Lu H, et al., "Phosphorothioate oligonucleotides inhibit human immunodeficiency virus type 1 fusion by blocking gp41 core formation", Antimicrob Agents Chemother. 2006 Apr;50(4):1393-401.

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