ANTIVIRALS THAT TARGET THE AMINO-TERMINAL DOMAIN OF HIV TYPE-1 GLYCOPROTEIN-41

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 amin o acids, residues 519-541) of HIV-1 gp41 is cytolytic to both human er ythrocytes (non-CD4(+) cells) and Hut-78 cells (CD4(+) lymphocytes), A ccordingly, FP-I-induced hemolysis may be used as a surrogate assay fo r evaluating the role of the N-terminal gp41 domain in HIV-cell intera ctions, Here, we studied the blocking of FP-I-induced lysis of erythro cytes 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 (ape A-1) and a peptide based on apo A-1, (3) dextran sulfate, (4) gp4 1 peptide (residues 637-666), and (5) anionic human serum albumins, Do se-response curves indicated that their relative potency in inhibiting FP-I-induced hemolysis was approximately correlated with their previo usly 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 vit ro antiviral activity and low cytotoxicity of these agents suggest tha t blocking membrane-FP-I interactions offers a novel approach for AIDS therapy or prophylaxis.