Antivirals that target the amino-terminal domain of HIV type 1 glycoprotein 41.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Antivirals that target the amino-terminal domain of HIV type 1 glycoprotein 41.

AIDS Res Hum Retroviruses. 1995 Jun;11(6):677-86. Unique Identifier : AIDSLINE MED/96078228
Gordon LM; Waring AJ; Curtain CC; Kirkpatrick A; Leung C; Faull K; Mobley PW; Department of Pediatrics, Drew University-King Medical; Center/UCLA 90059, USA.

Abstract: Functional and structural studies were made to assess whether a class of antiviral agents targets the N-terminal domain of the glycoprotein 41,000 (gp41) of human immunodeficiency virus type 1 (HIV-1). Previous experiments have shown that the amino-terminal peptide (FP-I; 23 amino acids, residues 519-541) of HIV-1 gp41 is cytolytic to both human erythrocytes (non-CD4+ cells) and Hut-78 cells (CD4+ lymphocytes). Accordingly, FP-I-induced hemolysis may be used as a surrogate assay for evaluating the role of the N-terminal gp41 domain in HIV-cell interactions. Here, we studied the blocking of FP-I-induced lysis of erythrocytes by the following anti-HIV agents: (1) IgG [i.e., anti-(518-541) IgG] raised to an immunoconjugate of Arg-FP-I, (2) apolipoprotein A-1 (apo A-1) and a peptide based on apo A-1, (3) dextran sulfate, (4) gp41 peptide (residues 637-666), and (5) anionic human serum albumins. Dose-response curves indicated that their relative potency in inhibiting FP-I-induced hemolysis was approximately correlated with their previously reported anti-HIV activity. Electron spin resonance (ESR) studies showed that FP-I spin labeled at the N-terminal alanine binds to anti-(518-541) IgG, dextran sulfate, and anionic albumins. The high in vitro antiviral activity and low cytotoxicity of these agents suggest that blocking membrane-FP-I interactions offers a novel approach for AIDS therapy or prophylaxis.

Keywords: Amino Acid Sequence Antibodies, Viral Antiviral Agents/*PHARMACOLOGY Apolipoprotein A-I/PHARMACOLOGY Dextran Sulfate/PHARMACOLOGY Erythrocyte Membrane/METABOLISM Erythrocytes Hemolysis Human HIV Envelope Protein gp41/CHEMISTRY/*DRUG EFFECTS/IMMUNOLOGY/ METABOLISM/PHARMACOLOGY HIV-1/*DRUG EFFECTS IgG/PHARMACOLOGY Immunoconjugates Molecular Sequence Data Peptide Fragments/CHEMISTRY/*DRUG EFFECTS/IMMUNOLOGY/METABOLISM/ PHARMACOLOGY Serum Albumin/PHARMACOLOGY Spin Labels Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE
960228
M9621022

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